Diabetes in Children and the Role of Micronutrients

Type 1 diabetes

Type 1 diabetes (known as insulin-dependent, juvenile or childhood-onset diabetes) is characterized by deficient insulin production in the pancreas,which requires daily administration of insulin. Symptoms include frequent urination, thirst, persistent hunger, weight loss, vision changes and fatigue, all of which may occur suddenly². Until not long ago, most children diagnosed with diabetes suffered from the type 1 form of the disease. Its incidence and prevalence had varied depending on the geographical region (Figure 1) and it was speculated that environmental factors could contribute to these differences³.

According to these data, type 1 diabetes is widespread among children in Finland and Sardinia and rather uncommon in China, India and Venezuela. Wide variations in disease occurrence have also been noted between neighboring areas in Europe and in North America. Finland, Germany and Norway have reported annual increases of type 1 diabetes in children. Barat reports that in France currently more than one quarter of children diagnosed with type 1 diabetes are under the age of 5⁴.

Continuing increase in type 1 diabetes incidence was also registered in the UK, where the  disease was shown to be more frequent in children than in young adults⁵.

In Europe, in general, the substantial increase in type 1 diabetes has been noted in  children younger than 5 years of age³.

Forecasts indicate that a doubling of new cases of type 1 diabetes in European children  younger than 5 years is predicted between 2005 and 2020, and that the incidence in  children younger than 15 years will rise by 70%⁶.

Figure 1. Incidence of type 1 diabetes in children aged 0-14 years, by geographical region and over time³.

Type 2 diabetes

Type 2 diabetes (also called non-insulin-dependent or adult-onset diabetes) results from the body’s ineffective response to insulin or its insufficient production. About 90% of people diagnosed with diabetes suffer from type 2². Although symptoms may be  similar to type 1 diabetes, they are often less pronounced. As a result, the disease may be diagnosed  several years after onset, once its complications have already arisen.

Until recently, this type of diabetes was seen mainly in adults, but now it is increasingly diagnosed in children². Experts estimate that type 2 diabetes in youth has grown from less than 5 percent in 1994 to about 20 percent of all newly diagnosed cases in recent years. Currently, about 45% of diabetes cases in adolescents are attributed to type 2 diabetes^7,8.

Type 1 diabetes

The exact causes of type 1 diabetes are largely unknown. Since type 1 diabetes is often inherited, it was speculated that genetics may play a pivotal role in its development. In most cases it is a result of an autoimmune condition in which the immune system damages the pancreatic cells which consequently cease producing a hormone, insulin. Other anticipated causes include:

Childhood vaccinations. The U.S. Centers for Disease Control (CDC) supports scientific studies by Classen, whose research concludes that vaccines can trigger type 1 diabetes. The evaluation of type 1 diabetes cases in relation to immunizations indicate an increase in the incidence of type 1 diabetes 2-4 years following the introduction of the MMR (measles, mumps, and rubella) and pertussis vaccines. Inversely, a decrease in type 1 diabetes was observed 3-4 years after the discontinuation of pertussis and BCG (Bacillus Calmette–Guérin) vaccines⁹. Classen and colleagues also evaluated whether Hemophilus influenza B (HiB) vaccine can be associated with an increased risk of type 1 diabetes. About 116,000 children born in Finland (October 1st, 1985 – August 31st, 1987) were randomized to receive 4 divided doses of the HiB vaccine (PPR-D, Connaught) starting at 3 months of life, or one dose starting after 24 months of life. A control-cohort included 128,500 children born in Finland in the 24 months prior to the HiB vaccine study. The results showed that exposure to HiB immunization was associated with an increased risk of type 1 diabetes¹⁰.

Low levels of vitamin D. The association between vitamin D deficiency and type 1 diabetes was studied in 185 children (9.8 years old on average) diagnosed with this disease. The subjects included 51% Caucasian, 25% Hispanic, 4% mixed-Hispanic, 4% African American, and 16% other/mixed race. The majority of these young diabetic patients had low vitamin D levels (40% showing vitamin D insufficiency, and 18% were vitamin D deficient). The study concluded that vitamin D deficiency is common at onset of pediatric type 1 diabetes¹¹. These findings corroborated with a metaanalysis study by Liu and colleagues, which concluded that serum vitamin D was significantly lower in children with type 1 diabetes than in healthy controls¹².

Type 2 diabetes

Development of type 2 diabetes has been largely associated with a global rise of childhood obesity. Numerous data show that healthy eating and lifestyle habits are a strong defense against this disease¹³.

Overweight. The increase in type 2 diabetes among children and adolescents has emerged in parallel with an alarming rise in overweight and obesity among youth (Figure 2). Increase in visceral fat has been implicated in developing the insulin resistance which often precedes type 2 diabetes¹⁴. A prospective cohort study conducted between 1965 and 2007 in 5,532 American Indian children showed that diabetes incidence was higher in overweight than in normal weight children¹⁵. These results, which corroborate data obtained in other populations and countries (WHO European Region), highlight the strong involvement of body weight and dietary habits in the development of diabetes in children.

Diet and food industry. The food industry has an important role in influencing children’s diets and their dietary choices. Due to food processing methods and modern agriculture our diet has become calorie rich and micronutrient poor. In addition, most processed foods advertised are targeted at and consumed by the young population and contain large amounts of sugar (i.e. soft drinks, cereals, snacks and ready-toeat meals), increasing the risk of diabetes.

Figure 2. Overweight prevalence among U.S. children and adolescents¹⁴.

Boulton and colleagues investigated the amount of sugars in juice drinks and smoothies marketed to children sold by seven major UK supermarkets. The results showed that the sugar content in these products is unacceptably high and the study concluded that manufacturers must stop adding unnecessary sugars and calories¹⁶ as a necessary measure to reduce the prevalence of overweight, obesity and type 2 diabetes¹⁷. Especially of concern is an increasing consumption of High Fructose Corn Syrup (HFCS), which, as an inexpensive ingredient, has become the most commonly used sweetener in processed foods. Its introduction parallels a rise in obesity, diabetes, hypertension and kidney disease^18,19, as the liver converts fructose into fat. It has been shown that as little as four weeks of a moderate fructose diet can increase blood cholesterol and glucose levels. Human and animal studies have shown that fructose can induce metabolic syndrome including insulin resistance, coronary microvascular disease, and oxidative stress. Interestingly these effects have not been seen in animals fed glucose or starch, which suggests that these mechanisms are not mediated by excessive caloric intake, but rather relate to fructose processing in the body²⁰.

Physical activity. The WHO defines “physical activity” as any bodily movement involving skeletal muscles that requires energy expenditure. This differs from “exercise”, which is a physical activity that is planned and structured. Insufficient physical activity is considered one of the 10 leading risk factors for death worldwide and a key risk factor for diabetes. According to the WHO, over 80% of the world’s adolescent population has insufficient physical activity^21,22.

Insufficient physical activity has also been linked to a higher risk of diabetes in children. A retrospective population-based survey in 2,720 adults (1,096 male and 1,624 female) showed that early sport practice during childhood and adolescence was associated with lower occurrence of type 2 diabetes and arterial hypertension later in adulthood²³. These data are supported by a prospective longitudinal study in 8 year old children (199 subjects) and in 12 year olds (107 children). The evaluation of anthropometric data, blood tests and physical activity in this population showed that physical activity improves insulin sensitivity and over time affects the levels of C-peptide (indicator of insulin production in the pancreas)²⁴.

Cognitive and behavioral impairment. Children and adolescents with type 1 diabetes³⁴ (Figure 3) and type 2 diabetes often display behavioral disorders and cognitive impairment. Jabbourand colleagues investigated barriers to active lifestyles in children with type 1 diabetes. They showed that among others a loss of control of diabetes, fear of hypoglycemia, work schedule, and low fitness levels were the most important barriers that affected children’s psychological balance³⁵. A group of researchers at the Cincinnati Children’s Hospital Medical Center assessed cognitive and behavioral performance in obese adolescents with type 2 diabetes and found they performed worse than controls³⁶.

Diabetic nephropathy. Diabetic nephropathy is defined as an abnormal urinary albumin excretion (macroalbuminuria). Suh and colleagues found that early stages of nephropathy in pediatric patients with type 1 diabetes can be detected by urinary tubular damage and inflammatory markers³⁷. A study in 56 patients with type 1 diabetes (mean age 13.1) and 49 healthy controls (mean age 12.8) evaluated serum NGAL (Neutrophil Gelatinase-Associated Lipocalin) and cystatin C (nephelometry), in addition to standard blood chemistry and urinary albumin excretion, at enrollment and after 12-15 months. The researchers suggested that NGAL and cystatin C, which are the markers of renal injury, may be used as supplementary tests to the urine albumin excretion for early detection of renal dysfunction in children³⁸. Between 2002 and 2013, the annual prevalence of diabetic nephropathy in pediatric patients with diabetes increased from 1.16 to 3.44% for all cases and was highest in patients aged 12 to 18 years of age^39,40.

Figure 3. Short and long term behavioral and cognitive reported alterations following type 1 diabetes mellitus onset in children and adolescents according to type 1 diabetes mellitus duration³⁴.

Diabetic neuropathy. Nerve damage represents the major complication in type 1 diabetes classified as polyneuropathy, focal neuropathy and autonomic neuropathy. The latter seems to be detectable even in asymptomatic children and adolescents with diabetes and is associated with the most serious consequences, such as unawareness of hypoglycemia and cardiovascular dysfunction⁴¹.

Diabetic retinopathy. Diabetic retinopathy is caused by damage to the blood vessels of the tissue at the back of the eye (retina), which at its early stages does not cause symptoms. A retrospective study of 143 children aged 12 or younger concluded that retinopathy screening should start at this young age⁴².

Juvenile arthritis. Juvenile arthritis is caused by inflammation of the joints. It has been shown that juvenile arthritis and diabetes end-points were considerably larger in pediatric patients with type 1 diabetes than in the general population⁴³.

Pediatric osteoporosis. Pediatric osteoporosis is characterized by low bone mass density (BMD). While in adults low BMD is generally due to net bone loss after its peak accrual, in children it can result from loss of bone or, more commonly, impaired bone mineralization. Endocrine disorders, such as diabetes can lead to pediatric osteoporosis⁴⁴.

Periodontal disease. Periodontal diseases are bacterial infections of the tissues surrounding and supporting the teeth. Gingivitis, an inflammation of the soft tissues only, can progress to periodontitis, where destruction of the connective tissue attachment and alveolar bone can eventually lead to tooth loss. Periodontal destruction in diabetes can start early in life and become more prominent as children become adolescents⁴⁵. Xavier et al. evaluated 168 children (13 +/- 3.5 years old) with type 1 diabetes for plaque index (PI), sites with bleeding on probing (BOP), probing depth (PD) and clinical attachment level (CAL) in all occlusion of permanent teeth. Gingivitis was diagnosed in 20.8% children and 5.9% children had periodontitis. The authors concluded that periodontal problems in this young population were significantly associated with the duration of type 1 diabetes and poor glycemic control⁴⁶.

Skin problems. Diabetes can affect every part of the body, including the skin. In fact, skin problems are sometimes the first sign of diabetes. Some of them, such as bacterial infections, fungal infections, and itching can affect anyone, but people with diabetes are more prone to them. Skin problems that develop mostly or exclusively in people with diabetes include diabetic dermopathy, necrobiosis lipoidicadiabeticorum, diabetic blisters, and eruptive xanthomatosis⁴⁷.

Digestive tract infections: Studies have shown frequent yeast-like fungi infections (e.g. Candida albicans) in the digestive tract of children with type 1 diabetes⁴⁸, which is resistant to conventional antifungal treatment⁴⁹ (Figure 4).

Conventional treatments

Insulin and metformin
The U.S. Food and Drug Administration (FDA)⁵⁰ has only approved the use of metformin and insulin in children (FDA). Insulin is administered in children with type 1 diabetes, while insulin together with metformin can be prescribed to children with type 1 and type 2 diabetes.

Figure 4. Comparison of Candida albicans strains susceptible, intermediate, and resistant to the six tested antifungal drugs in children with type 1 diabetes mellitus (A) and healthy control subjects (B)⁴⁹.

Insulin. The first option in the treatment of type 1 diabetes is a hormone, insulin, which regulates serum glucose by increasing its uptake into muscle and adipose tissue and decreases glucose production in the liver. The following insulin products are indicated for the use in children: Aspart, Glulisine, Lispro, Detemir, and Glargine⁵¹.

The administration of insulin is not risk-free as it is associated with a risk of hypoglycemia, peripheral hyperinsulinemia, headache, and weight gain. A recent Italian study which investigated the effects of Detemir in 15 pre-pubertal children with type 1 diabetes showed that this treatment was associated with an abnormal body weight not related to pubertal growth⁵².

The delivery of insulin not by injection, but by a pump, is often encouraged in children and adolescents. Pumps deliver insulin 24 hours a day through a catheter placed under the skin.This is more convenient for a patient and allows for better control of blood sugar. However, there were reports of pump-related adverse events in children 1–12 years old. From January 1, 1996, through December 31, 2009, a total of 21,769 reports were collected for all ages. Of these, 1,774 were for children aged 1–12 years and more than half resulted in serious outcomes (Table 1). Children were hospitalized for hyperglycemia or hypoglycemia and deaths of five patients were reported⁵³.

Table 1. Summary of FDA insulin pump adverse event reports for ages 1-12 years, January 1, 1996, through December 31, 2009⁵³.

Metformin. Metformin, a drug classified as a biguanide, is the first option in the treatment of type 2 diabetes in pediatrics. It works by reducing glucose production and activating glucose uptake in peripheral tissues. The administration of metformin can cause various side effects, such as decreased appetite, diarrhea, muscle pain, and gastrointestinal problems⁵⁴.

Metformin together with insulin has also been used in the treatment of type 1 diabetes. In a study in 140 overweight adolescents with type 1 diabetes the use of metformin as an adjunct to insulin did not improve glycemic control and led to an increased risk of gastrointestinal adverse events⁵⁵. Another study investigated the prevalence of chronic diarrhea in 861 patients with type 1 and type 2 diabetes taking metformin. The authors concluded that chronic diarrhea is often associated with diabetes and the most common cause of non-diabetic diarrhea is metformin⁵⁶.

Other conventional therapies
Although the FDA has only approved metformin and insulin in diabetic children and adolescents, some physicians recommend the use of drugs which have been approved for adults⁵⁷. These often lack clinical evidence of their efficacy in a pediatric population, which makes young patients prone to unexpected health risks⁵¹. A short review of these treatment options is presented below:

Thiazolidinediones(TZDs). This class of drugs, which has not been approved in children, works by increasing insulin sensitivity in the cells. Wen and colleagues examined the potentially inappropriate prescription of TZDs in different groups of patients, including young people under 18 years of age. Data collected from Taiwan’s National Health Insurance data set from 2001 to 2006 showed that inappropriate prescription of TZDs actually increased from 9.41% in 2001 to 12.50% in 2006⁵⁸. The use of TZDs decreased after a black-box warning was issued in 2007 for a drug, rosiglitazone, highlighting its cardiovascular risks⁵⁹.

Recently, the short-term use of rosiglitazone was evaluated in a pilot study in 21 obese adolescents (13 to 18 years old) with impaired glucose tolerance. The study found that 58% of patients treated with rosiglitazone returned to normal glucose tolerance, compared to 44% of patients taking placebo. Although few adverse events surfaced during this treatment, the authors concluded that, given the cardiovascular concerns with rosiglitazone in adults and the small pool of data on its use in children, it would be premature to recommend rosiglitazone in children⁶⁰.

Sulfonylureas. Sulfonylureas promote insulin secretion by acting on pancreatic β cells⁶⁰. They are not labeled for pediatric use and data on their use in children are limited.

The University Group Diabetes Program clinical trial has reported an association between the administration of the sulfonylurea drug, tolbutamide, and increased cardiovascular mortality. This provided the basis for the FDA warning about “increased risk of cardiovascular mortality” for this and other oral sulfonylurea hypoglycemic drugs⁶¹.

Amylin analog (Pramlintide). It is a synthetic analog of human amylin, a hormone that acts together with insulin to delay gastric emptying and inhibit release of glucagon, a hormone that raises the level of glucose in the blood. According to the FDA this drug has not been sufficiently studied in children but some doctors apply it off-label. Clinical evidence on the use of pramlintide in children is limited to type 1 diabetes and to small studies enrolling only 8 to 13 patients. In one of the studies, 10 adolescents 13 to 17 years of age were randomized to active treatment with 15 mcg of pramlintide before meals (titrated to 30 mcg if tolerated) or to control for 28 days. This preliminary study led to improvements in HbA1c, body weight, and insulin dose in adolescents with type 1 diabetes. However, the package insert for this drug contains a black box warning regarding risk of severe hypoglycemia in type 1 diabetes. The most common adverse events include hypoglycemia, nausea, headache, anorexia, and abdominal pain⁶⁰.

Other drugs, such as Incretin based therapies: dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists as well as Meglitinides and Alpha glucosidase inhibitors were not approved for use in children⁶⁰.

Vitamin C plays a special role in diabetes due to its structural similarity to sugar (glucose) and the use of common intracellular transporters, GLUT1 and GLUT3, by both compounds. As a consequence, elevated glucose levels promote vitamin C deficiency inside the cells by competing with vitamin C for its intracellular entry. This has particularly detrimental consequences for the cardiovascular system in diabetic patients. High glucose related vitamin C deficiency inside the blood vessel wall cells impairs collagen production, thereby compromising vascular integrity and accelerating atherosclerosis as well as microvascular dysfunctions in different organs in diabetic patients (Figure 5)²⁵. Moreover, it has been shown that insufficient ascorbate levels in red blood cells in diabetes promote rigidity of these cells, thereby contributing to microvascular angiopathy⁷⁹. In addition to impaired intracellular transport, inadequate vitamin C status in diabetic patients is prompted by higher urinary losses of this vitamin and increased metabolic turnover, all contributing to increased dietary requirements for vitamin C in diabetic patients.

Most clinical aspects of vitamin C in diabetes have been evaluated in adults^80,81 and confirm compromised vitamin C status, including low vitamin C levels in type 2 diabetic patients with more severe diabetic nephropathy⁸². A study in 84 patients with type 2 diabetes receiving different doses of vitamin C for six weeks showed that its intake at a level of 1,000 mg a day may be beneficial in decreasing blood glucose and lipid levels, thus reducing the risk of vascular complications⁸³. A recent study with 2,025 children aged 9-10 years investigated the relationship between vitamin C blood levels, fruit and vegetable intakes and insulin resistance. Based on a 24h dietary recall it was found that lower plasma vitamin C levels were associated with insulin resistance in these young individuals⁸⁴.

Figure 5. Vitamin C Supplementation is an essential measure for diabetic patients in preventing cardiovascular disease²⁵.

Vitamin D
Vitamin D is a fat-soluble vitamin mostly known for facilitating calcium absorption. However this vitamin also affects cell growth, inflammation and various neuromuscular and immune functions. The best sources are fatty fish (salmon, tuna, and mackerel) and fish liver oils. Small amounts of vitamin D are found in beef liver, cheese, and egg yolks⁸⁵.

The majority of epidemiological studies have demonstrated an association between low vitamin D and insulin resistance and/or type 2 diabetes mellitus. Also, the study in young patients with type 1 diabetes showed that over 95% of them had insufficient (20-30 ng/mL) or deficient (86. The association between vitamin D levels (25(OH)D) and HbA1c was confirmed in 197 diabetic children and adolescents with type 1 diabetes, showing a high prevalence of low vitamin D status in association with type 1 diabetes⁸⁷. Treatment of 53 pediatric type 1 diabetes patients with vitamin D3 for three months demonstrated better glycemic control and a statistically significant reduction in HbA1C⁸⁸.

Vitamin D deficiency has been also associated with diabetic peripheral neuropathy⁸⁹. In the pediatric populationits prevalence ranges from 7% to 54% depending on the diagnostic criteria used, but vitamin D subclinical manifestations occur in about 57% children and adolescents with type 1 diabetes⁴¹. In addition, a study of 517 children and adolescents with type 1 diabetes showed that vitamin D deficiency can double the risk of developing retinopathy⁹⁰.

Vitamin K
Vitamin K is a generic name for a family of quinone compounds such asphylloquinone (vitamin K1) and a series of menaquinones (vitamin K2). Vitamin K functions as a coenzyme for vitamin K-dependent carboxylase, required for the synthesis of proteins involved in hemostasis and bone metabolism and other physiological functions. Best sources of vitamin K1 include vegetables, especially green leafy vegetables, vegetable oils, and some fruits. Meat, dairy foods and eggs contain low levels of vitamin K1, but modest amounts of vitamin K2⁹¹.

It was reported that vitamin K supplementation has beneficial effects in improving insulin sensitivity⁹². Both animal and human studies have suggested that a beneficial function of vitamin K in insulin sensitivity and glucose tolerance may be mediated by its regulation of cytokines secreted by adipose tissue, its anti-inflammatory properties and lipid-lowering effects⁹³. In a 3 year randomized, double-blind, placebo controlled trial of 355 patients, vitamin K significantly improved insulin sensitivity in men with diabetes by interfering with pancreatic β-cell proliferation, insulin sensitivity, production of adiponectin, and glucose tolerance⁹⁴. Vitamin K effects were not evaluated in diabetic pediatric population.

Micronutrient synergy and its application in young organisms with diabetes

Biological effects of micronutrients largely depend on mutual interactions and cooperation with other natural components in numerous complex cellular metabolic pathways. The new approach in dietary supplementation developed at the Dr. Rath Research Institute and introduced as “micronutrient synergy” allows for application of specific combinations of micronutrients in a controlled way. Synergy allows for expanded metabolic efficacy of micronutrients by simultaneously targeting several cellular mechanisms associated with various pathologies and enhanced efficacy with lower doses of individual components. Micronutrient synergy presents a new strategy in developing effective natural approaches against various human pathologies, including diabetes.

An in vivo study conducted in young mice with diabetes showed that a specific micronutrient synergy was superior to a diabetes drug, metformin, in regulating blood sugar levels and other aspects of diabetes¹⁵⁰. Diabetes was induced in these young mice by feeding them a fructose-rich diet, which indicates its relevance to the effects of high fructose consumption in youth and adolescence. Fructose-induced protein damage was evaluated by measuring serum levels of fructosamine, a marker of protein damage in diabetes. The results showed that dietary intake of the synergistic micronutrient complex reduced serum fructosamine by about 4%, while metformin caused its 15.9% increase (Figure 6). In addition, insulin blood levels in mice in the micronutrient supplemented group were restored to normal values, while the metformin group had reduced insulin. In addition, micronutrient supplementation showed to be beneficial in reducing the risk of cardiovascular disease in these animals by lowering blood pressure, total cholesterol, and counteracting other negative effects of fructose¹⁵⁰. These results indicate that synergistically interacting micronutrient composition results in more comprehensive anti-diabetic effects than individual compounds.

Figure 6. Comparative effects of metformin and diabetic nutrient mixture on fructosamine levels in fructose-fed mice. The DNM group demonstrated significantly lower fructosamine concentration (3.94% decrease) than the control (fructose-only fed) group, whereas the MET- treated group showed a 15.9% increase in fructosamine compared to the control. A t-test performed between the DNM group vs the fructose alone group and ANOVA for all groups yielded p<0.05¹⁵⁰.

References

1. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med, 2006, 3(11):e442. www.ncbi.nlm.nih.gov/pubmed/17132052

2. WHO, World Health Organization. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus. Geneva, World Health Organization, 1999.

3. Atkinson M, Eisenbarth GS, Michels AW. Type 1 diabetes. Lancet. 2014 Jan 4; 383(9911): 69–82. www.ncbi.nlm.nih.gov/pmc/articles/PMC4380133

4. Barat P. Epidemiology of type 1 diabetes in children. SoinsPediatrPueric. 2016 Jan- Feb;(288):10-2. www.ncbi.nlm.nih.gov/pubmed/26776685

5. Imkampe AK, Gulliford MC. Trends in Type 1 diabetes incidence in the UK in 0- to 14-year-olds and in 15- to 34-year-olds, 1991-2008. Diabet Med. 2011 Jul;28(7):811-4. www.ncbi.nlm.nih.gov/pubmed/21395679

6. Patterson CC, Dahlquist GG, Gyürüs E, Green A, Soltész G; EURODIAB Study Group. Incidence trends for childhood type 1 diabetes in Europe during 1989-2003 and predicted new cases 2005-20: a multicentre prospective registration study. Lancet. 2009 Jun 13;373(9680):2027-33. www.ncbi.nlm.nih.gov/pubmed/19481249/

7. Pinhas-Hamiel O Zeitler P. The global spread of type 2 diabetes mellitus in children and adolescents. J Pediatr 2005;146:693–700. www.ncbi.nlm.nih.gov/pubmed/15870677

8. Pinhas-Hamiel O, Zeitler P. Acute and chronic complications of type 2 diabetes mellitus in children and adolescents. Lancet 2007;369:1823–1831. www.ncbi.nlm.nih.gov/pubmed/17531891

9. Classen JB, Classen DC. Clustering of cases of type 1 diabetes mellitus occurring 2-4 years after vaccination is consistent with clustering after infections and progression to type 1 diabetes mellitus in autoantibody positive individuals. J PediatrEndocrinolMetab. 2003 Apr- May;16(4):495-508. www.ncbi.nlm.nih.gov/pubmed/12793601

10. Classen JB, Classen DC. Clustering of cases of insulin dependent diabetes (IDDM) occurring three years after hemophilus influenza B (HiB) immunization support causal relationship between immunization and IDDM. Autoimmunity. 2002 Jul;35(4):247-53. www.ncbi.nlm.nih.gov/pubmed/12482192

11. Al-Zubeidi H, Leon-Chi L, Newfield RS. Low vitamin D level in pediatric patients with new onset type 1 diabetes is common, especially if in ketoacidosis. Pediatr Diabetes. 2015 Dec 23. www.ncbi.nlm.nih.gov/pubmed/26694737

12. Liu C et al. Correlation of serum vitamin d level with type 1 diabetes mellitus in children: a meta- analysis. Nutr Hosp. 2015 Oct 1;32(4):1591-4. www.ncbi.nlm.nih.gov/pubmed/26545522

13. WHO, World Health Organization. What are the risk of diabetes in children? www.who.int/features/qa/65/en/

14. Copeland C, Becker D, Gottschalk M, Hale D. Type 2 Diabetes in Children and Adolescents: Risk Factors, Diagnosis, and Treatment. Clinical Diabetes 2005 Oct; 23(4): 181-185. www.clinical.diabetesjournals.org/content/23/4/181

15. Wheelock KM, Sinha M, Knowler WC, Nelson RG, Fufaa GD, Hanson RL. Metabolic Risk Factors and Type 2 Diabetes Incidence in American Indian Children J ClinEndocrinolMetab. 2016 Feb 25:jc20154309. www.ncbi.nlm.nih.gov/pubmed/26913636

16. Boulton J, Hashem KM, Jenner KH, Lloyd- Williams F, Bromley H, Capewell S. How much sugar is hidden in drinks marketed to children? A survey of fruit juices, juice drinks and smoothies. BMJ Open. 2016 Mar 23;6(3):e010330. www.ncbi.nlm.nih.gov/pubmed/27009146

17. Ma Y, He FJ, Yin Y, Hashem KM, MacGregor GA. Gradual reduction of sugar in soft drinks without substitution as a strategy to reduce overweight, obesity, and type 2 diabetes: a modelling study. Lancet Diabetes Endocrinol. 2016 Feb;4(2):105-14. www.ncbi.nlm.nih.gov/pubmed/26777597

18. Johnson RJ, Segal MS, Sautin Y. Potential role of sugar (fructose) in the epidemic of hypertension, obesity and the metabolic syndrome, diabetes, kidney disease, and cardiovascular disease. Am J ClinNutr 2007;86(4):899–906. www.ncbi.nlm.nih.gov/pubmed/17921363

19. Segal MS, Gollub E, Johnson RJ. Is the fructose index more relevant with regards to cardiovascular disease than the glycemic index? Eur J Nutr 2007;46(7):406–17. www.ncbi.nlm.nih.gov/pubmed/17763967

20. Nakagawa T et al. A causal role for uric acid in fructose-induced metabolic syndrome. Am J Physiol 2006;290(3): F625–31. www.ncbi.nlm.nih.gov/pubmed/16234313

21. WHO, Word Health Organization European Region. Data and statistics. www.euro.who.int/en/health-topics/noncommunicable-diseases/obesity/data-and-statistics

22. WHO, World Health Organization. Physical activity. www.who.int/mediacentre/factsheets/fs385/en/

23. Fernandes RA, Zanesco A. Early sport practice is related to lower prevalence of cardiovascular and metabolic outcomes in adults independently of overweight and current physical activity. Medicina (Kaunas). 2015;51(6):336-42. www.ncbi.nlm.nih.gov/pubmed/26739675

24. Huus K, Åkerman L, Raustorp A, Ludvigsson J. Physical Activity, Blood Glucose and C-Peptide in Healthy School-Children, a Longitudinal Study. PLoS One. 2016 Jun 7;11(6):e0156401. www.ncbi.nlm.nih.gov/pubmed/27270732

25. Rath M. Why animals don´t get heart attack but people do! Chapter 7: Diabetes, 2003.

26. Chrysis D, Efthymiadou A, Mermigka A, Kritikou D, Spiliotis BE. Osteoprotegerin, RANKL, ADMA, and Fetuin-A serum levels in children with
type I diabetes mellitus. Pediatr Diabetes. 2016 Mar 29. www.ncbi.nlm.nih.gov/pubmed/27028343

27. Song SH, Hardisty CA. Early-Onset Type 2
Diabetes Mellitus: An Increasing Phenomenon of Elevated Cardiovascular Risk. Expert Rev CardiovascTher. 2008;6(3):315-322. www.medscape.com/viewarticle/573459

28. al-Naama LM, Kadhim M, al-Aboud MS. Lipid profile in children with insulin dependent diabetes mellitus. J Pak Med Assoc. 2002
Jan;52(1):29-34. www.ncbi.nlm.nih.gov/pubmed/11963582

29. Petitti DB et al. Serum lipids and glucose control: the SEARCH for Diabetes in Youth study. Arch PediatrAdolesc Med. 2007 Feb;161(2):159-65. www.ncbi.nlm.nih.gov/pubmed/17283301

30. Reinehr T et al. Inflammatory Markers in Obese Adolescents with Type 2 Diabetes and Their Relationship to Hepatokines and Adipokines.J Pediatr. 2016 Mar 17. www.ncbi.nlm.nih.gov/pubmed/26996723

31. Freemark M, Levitsky L. Screening for Celiac Disease in Children with Type 1 Diabetes. Diabetes Care 2003 Jun; 26(6): 1932-1939. http://care.diabetesjournals.org/content/26/6/1932

32. Kordonouri O, Hartmann R, Deiss D, Wilms M, Gruters-Kieslich A. Natural course of autoimmune thyroiditis in type 1 diabetes: association with gender, age, diabetes duration, and puberty. Arch Dis Child. 2005 Apr; 90(4): 411–414. www.ncbi.nlm.nih.gov/pmc/articles/PMC1720371/

33. Lu MC, Chang SC, Huang KY, Koo M, Lai NS.
Higher Risk of Thyroid Disorders in Young Patients with Type 1 Diabetes: A 12-Year Nationwide, Population-Based, Retrospective Cohort Study. PLoS One. 2016 Mar
23;11(3):e0152168. www.ncbi.nlm.nih.gov/pubmed/27007574

34. Litmanovitch E, Geva R, Rachmiel R. Short and long term neuro-behavioral alterations in type 1 diabetes mellitus pediatric population. World J Diabetes. 2015 Mar 15; 6(2): 259–270. www.ncbi.nlm.nih.gov/pmc/articles/PMC4360419/

35. Jabbour G, Henderson M, Mathieu ME. Barriers to Active Lifestyles in Children with Type 1 Diabetes. Can J Diabetes. 2016 Apr;40(2):170-2. www.ncbi.nlm.nih.gov/pubmed/27038139

36. Brady CC et al. Obese adolescents with type 2 diabetes perform worse than controls on cognitive and behavioral assessments. Pediatr Diabetes. 2016 Mar 29. www.ncbi.nlm.nih.gov/pubmed/27028236

37. Suh JS et al.Urinary markers in the early stage of nephropathy in patients with childhood-onset type 1 diabetes. PediatrNephrol. 2016 31(4):623-31. www.ncbi.nlm.nih.gov/pubmed/26525196

38. Papadopoulou-Marketou N et al.NGAL and cystatin C: two possible early markers of diabetic nephropathy in young patients with type 1 diabetes mellitus: one year follow up. Hormones (Athens). 2015 Apr-Jun;14(2):232-40. www.ncbi.nlm.nih.gov/pubmed/25402375

39. Craig EM, Craig J, DabeleaD,Balde N, Seth A, Donaghue KC. ISPAD Clinical Practice Consensus Guidelines 2014 Compendium. Definition, epidemiology, and classification of diabetes in children and adolescents. http://onlinelibrary.wiley.com/doi/10.1111/pedi.12186/abstract

40. Li L, Jick S, Breitenstein S, Michel A. Prevalence of Diabetes and Diabetic Nephropathy in a Large U.S. Commercially Insured Pediatric Population,
2002–2013. Diabetes Care 2016 Feb; 39(2):278-284. http://care.diabetesjournals.org/content/39/2/278

41. Trotta D, Verrotti A, Salladini C, Chiarelli F.
Diabetic neuropathy in children and adolescents. Pediatr Diabetes. 2004 Mar;5(1):44-57. http://www.ncbi.nlm.nih.gov/pubmed/15043690

42. Hamid A, Wharton HM, Mills A, Gibson JM, Clarke M, Dodson PM. Diagnosis of retinopathy in children younger than 12 years of age: implications for the diabetic eye screening guidelines in the UK. Eye (Lond). 2016 Apr 15. http://www.ncbi.nlm.nih.gov/pubmed/27080488

43. Hermann G et al. Comorbidity of Type 1 Diabetes and Juvenile Idiopathic Arthritis. April 2015 Volume 166, Issue 4, Pages 930–935.e3. http://www.jpeds.com/article/S0022-3476(14)01195-0/fulltext

44. Mantravadi M. Pediatric Osteoporosis, 2016. http://emedicine.medscape.com/article/985221-overview#a3

45. Lalla E et al. Periodontal Changes in Children and Adolescents With Diabetes. Diabetes Care 2006 Feb; 29(2): 295-299. http://care.diabetesjournals.org/content/29/2/295

46. Xavier AC, Silva IN, Costa Fde O, Corrêa DS. Periodontal status in children and adolescents with type 1 diabetes mellitus. Arq Bras EndocrinolMetabol. 2009 Apr;53(3):348-54. http://www.ncbi.nlm.nih.gov/pubmed/19578597

47. American Diabetes Association. Skin Complications. www.diabetes.org/living-with-diabetes/complications/skin-complications

48. Kowalewska B, Kawko M, Zorena K, Myśliwiec M. Yeast-like fungi in the gastrointestinal tract in children and adolescents with diabetes type 1. PediatrEndocrinol Diabetes Metab. 2015;20(4):170-7. http://www.ncbi.nlm.nih.gov/pubmed/26615584

49. Kowalewska B, Zorena K, Szmigiero-Kawko M, Wąż P, Myśliwiec M. Higher diversity in fungal species discriminates children with type 1 diabetes mellitus from healthy control. Patients Prefer Adherence. 2016; 10:591-599. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4844445/

50. FDA, Food and Drug administration. Code of Federal Regulation. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=310.517

51. Onge ES, Miller SA, Motycka C, DeBerry A. A review of the treatment of type 2 diabetes in children. J PediatrPharmacolTher. 2015 Jan-Feb;20(1):4-16. http://www.ncbi.nlm.nih.gov/pubmed/25859165

52. Cherubini V, Pintaudi B, Iannilli A, Pambianchi M, Ferrito L, Nicolucci A. Long-acting Insulin Analogs Effect on gh/igf Axis of Children with Type 1 Diabetes: a Randomized, Open-label, Two-period, Cross-over Trial. ExpClinEndocrinol Diabetes. 2016 Mar 29. http://www.ncbi.nlm.nih.gov/pubmed/27023008

53. Cope JU, Samuels-Reid JH, Morrison AE. Pediatric Use of Insulin Pump Technology: A Retrospective Study of Adverse Events in Children Ages 1–12 Years J Diabetes Sci Technol.2012 Sep; 6(5): 1053–1059. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570839/

54. Gao YQ , Gao M, Xue Y. Treatment of diabetes in children. ExpTher Med. 2016 Apr;11(4):1168-1172 http://www.ncbi.nlm.nih.gov/pubmed/27073417

55. Libman IM et al. Effect of Metformin Added to Insulin on Glycemic Control Among Overweight/ Obese Adolescents With Type 1 Diabetes: A Randomized Clinical Trial. JAMA. 2015 Dec 1;314(21):2241-50. http://www.ncbi.nlm.nih.gov/pubmed/26624824

56. Lysy J, Israeli E, Goldin E. The prevalence of chronic diarrhea among diabetic patients. Am J Gastroenterol. 1999 Aug;94(8):2165-70.

57. Pozzo AM. Pediatric Type 2 Diabetes Mellitus Medication. Medscape, May 2014. http://reference.medscape.com/article/925700-medication

58. Wen YW, Tsai YW, Huang WF, Hsiao FY, Chen PF.The potentially inappropriate prescription of new drug: thiazolidinediones for patients with type II diabetes in Taiwan. Pharmacoepidemiol Drug Saf. 2011 Jan;20(1):20-9. http://www.ncbi.nlm.nih.gov/pubmed/21182151

59. Ahuja V, Chou CH. Novel Therapeutics for Diabetes: Uptake, Usage Trends, and Comparative Effectiveness. CurrDiab Rep. 2016 Jun;16(6):47. http://www.ncbi.nlm.nih.gov/pubmed/27076180

60. Onge ES, Miller SA, Motycka C, DeBerry A. A review of the treatment of type 2 diabetes in children. J PediatrPharmacolTher. 2015 Jan-Feb;20(1):4-16. http://www.ncbi.nlm.nih.gov/pubmed/25859165

61. FDA, Food and Drug administration. Code of Federal Regulation. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=310.517

62. Yaffe S. Rational Therapeutics for Infants and Children: Workshop Summary. Similarities and Dissimilarities in Physiology, Metabolism, and Disease States and Responses to Therapy in Children and Adults. National Academies Press (US); 2000.

63. Hines RN. Ontogeny of human hepatic cytochromes P450. J BiochemMolToxicol 21:169–175, 2007. http://onlinelibrary.wiley.com/doi/10.1002/jbt.20179/abstract

64. Sahota PS, Popp JA, Hardisty JF, Gopinath G. Toxicologic pathology non clinical safety assessment. Exocrine pancreas. 2013 CRC Press, Taylor & Francis Group.

65. Ulrich AB, Standop J, Schmied BM, Schneider MB, Lawson TA, Pour PM. Species Differences in the Distribution of Drug-Metabolizing Enzymes in the Pancreas. Toxicologic Pathology, vol 30, no 2, pp 247–253, 2002. http://tpx.sagepub.com/content/30/2/247

66. WHO, World Health Organization.Micronutrients.
http://www.who.int/nutrition/topics/micronutrients/en/

67. Dr. Rath Research Institute www.drrathresearch.org

68. NIH, National Institutes of Health. Vitamin A Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/VitaminA-HealthProfessional/

69. Meerza D, Iqbal S, Zaheer S, Naseem I. Retinoids have therapeutic action in type 2 diabetes. Nutrition 2016 Jul-Aug;32(7-8):898-903. http://www.ncbi.nlm.nih.gov/pubmed/27134203

70. Iqbal S, Naseem I. Role of vitamin A in type 2 diabetes mellitus biology: Effects of intervention therapy in a deficient state. Nutrition. July– August, 2015 Volume 31, Issues 7-8, Pages 901–907. http://www.nutritionjrnl.com/article/S0899-9007(14)00552-8/fulltext

71. Trasino SE, Benoit DY, Gudas LJ. Vitamin A Deficiency Causes Hyperglycemia and Loss of Pancreatic β-Cell Mass. J BiolChemistry. 2015, 290(3), 1456-1473. http://www.ncbi.nlm.nih.gov/pubmed/25451926

72. NIH, National Institutes of Health. Vitamin B12 Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/

73. Kibirige D, Mwebaze R. Vitamin B12 deficiency among patients with diabetes mellitus: is routine screening and supplementation justified? J. DiabMetab Disorders 2013; 12:7. https://jdmdonline.biomedcentral.com/articles/10.1186/2251-6581-12-17

74. Ho M et al. Vitamin B12 in obese adolescents with clinical features of insulin resistance. Nutrients. 2014 Dec 4;6(12):5611-8. https://www.ncbi.nlm.nih.gov/pubmed/25486369

75. Damião CP et al. Prevalence of vitamin B12 deficiency in type 2 diabetic patients using metformin: a cross-sectional study. Sao Paulo Med J. 2016 Jun 3. http://www.ncbi.nlm.nih.gov/pubmed/27276084

76. Akinlade KS, Agbebaku SO, Rahamon SK, Balogun WO. Vitamin B12 levels in patients with type 2 diabetes mellitus on metformin. Ann IbPostgrad Med. 2015 Dec;13(2):79-83. http://www.ncbi.nlm.nih.gov/pubmed/27162518

77. Dekelbab B, Kakkannat A. Prevalence of Vitamin B12 Deficiency in Children and Adolescents Treated with Metformin. Endocrine Society’s
96th Annual Meeting and Expo, June 21–24, 2014 – Chicago.

78. NIH, National Institutes of Health. Vitamin C Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/VitaminC-HealthProfessional/#h2

79. Tu H et al. Low Red Blood Cell Vitamin C Concentrations Induce Red Blood Cell Fragility: A Link to Diabetes Via Glucose, Glucose Transporters, and Dehydroascorbic Acid. EBioMedicine. 2015 Oct 3;2(11):1735-50. http://www.ncbi.nlm.nih.gov/pubmed/26870799

80. Li L, Jick S, Breitenstein S, Michel A. Prevalence of Diabetes and Diabetic Nephropathy in a Large U.S. Commercially Insured Pediatric Population,
2002–2013. Diabetes Care 2016 Feb; 39(2): 278-284. http://care.diabetesjournals.org/content/39/2/278

81. Christie-David DJ, Girgis CM, Gunton JE.
Effects of vitamin C and D in type 2 diabetes mellitus, Nutr and Dietary Suppl 2015, 15(7), 21-28. www.researchgate.net/publication/272092706_Effects_of_vitamins_C_and_D_in_type_2_diabetes_mellitus

82. Chou ST, Tseng ST. Oxidative stress markers in type 2 diabetes patients with diabetic nephropathy. ClinExpNephrol. 2016 May 27. http://www.ncbi.nlm.nih.gov/pubmed/27233502

83. ArdekaniMA ,Ardekani AS. Effect of vitamin C on blood glucose, serum lipids & serum insulin in type II diabetes patients. Indian J Med Research, vol. 126, no. 5, pp. 471–474, 2007. http://www.ncbi.nlm.nih.gov/pubmed/18160753

84. Donin AS et al. Fruit, vegetable and vitamin C intakes and plasma vitamin C: cross-sectional associations with insulin resistance and glycaemia in 9-10 year-old children. Diabet Med. 2016 Mar;33(3):307-15. http://www.ncbi.nlm.nih.gov/pubmed/26498636

85. NIH, National Institutes of Health. Vitamin D Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/

86. Mosso C, Hodgson MI, Ortiz T, Reyes ML.
Bone mineral density in young Chilean patients with type 1 diabetes mellitus. J PediatrEndocrinolMetab. 2016 Jun 1;29(6):731-6. http://www.ncbi.nlm.nih.gov/pubmed/27054593

87. Al Sawah S, Compher CW, Hanlon AL, Lipman TH. 25-Hydroxyvitamin D and glycemic control: A cross-sectional study of children and adolescents with type 1 diabetes. Diabetes Res ClinPract. 2016 May;115:54-9. http://www.ncbi.nlm.nih.gov/pubmed/27242123

88. Mohammadian S, Fatahi N, Zaeri H, Ali Vakili M. Effect of Vitamin D3 supplement in glycemic control of pediatrics with type 1 diabetes mellitus and vitamin D deficiency.J Clin Diagn Res 2015, 9(3), SC05-SC07. https://www.ncbi.nlm.nih.gov/pubmed/25954674

89. He R et al. Vitamin D deficiency increases the risk of peripheral neuropathy in Chinese patients with Type 2 diabetes. Diabetes Metab Res Rev. 2016 May 7. http://www.ncbi.nlm.nih.gov/pubmed/27155442

90. Kaur H et al. Vitamin D deficiency is associated with retinopathy in children and adolescents with type 1 diabetes. Diabetes Care. 2011 Jun;34(6):1400-2. https://www.ncbi.nlm.nih.gov/pubmed/21515836

91. NIH, National Institutes of Health. Vitamin K Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/VitaminK-HealthProfessional/#h3

92. Choi HJ et al. Vitamin K2 supplementation improves insulin sensitivity via osteocalcin metabolism: a placebo-controlled trial. Diabetes Care. 2011 Sep;34(9):e147. https://www.ncbi.nlm.nih.gov/pubmed/21868771

93. Manna P, Kalita J. Beneficial role of vitamin K supplementation on insulin sensitivity, glucose metabolism, and the reduced risk of type 2 diabetes: A review. Nutrition. 2016 Jul-Aug;32(7-8):732-9. http://www.ncbi.nlm.nih.gov/pubmed/27133809

94. DiNicolantonio JJ, Bhutani J, O’Keefe JH. The health benefits of vitamin K. Open Heart. 2015 Oct 6;2(1):e000300. http://www.ncbi.nlm.nih.gov/pubmed/26468402

95. NIH, National Institutes of Health. Chromium Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/Chromium-HealthProfessional/

96. Karagun BS et al.Chromium levels in healthy and newly diagnosed type 1 diabetic children. Pediatr Int. 2012 54(6):780-785. https://www.ncbi.nlm.nih.gov/pubmed/22783884

97. McIver DJ, Grizales AM, Brownstein JS, Goldfine AB. Risk of Type 2 Diabetes Is Lower in US Adults Taking Chromium-Containing Supplements. J Nutr. 2015 Dec;145(12):2675-82. http://www.ncbi.nlm.nih.gov/pubmed/26446484

98. NIH, National Institutes of Health. Iron Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/Iron-HealthProfessional/

99. Mojs E, Stanisławska-Kubiak M, Wójciak RW, Wojciechowska J, Przewoźniak S. Reduced iron parameters and cognitive processes in children and adolescents with DM1 compared to those with standard parameters. J Investig Med. 2016 Mar;64(3):782-5. http://www.ncbi.nlm.nih.gov/pubmed/26912011

100. NIH, National Institutes of Health. Magnesium Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/

101. Lin CC, Tsweng GJ, Lee CF, Chen BH, Huang YL. Magnesium, zinc, and chromium levels in children, adolescents, and young adults with type 1 diabetes. Clin. Nutr2016; 35, 880-884. https://www.ncbi.nlm.nih.gov/pubmed/26096861

102. Galli-Tsinopoulou A et al. Association between magnesium concentration and HbA1c in children and adolescents with type 1 diabetes mellitus. J Diabetes, 2014; 6(4), 369-377. https://www.ncbi.nlm.nih.gov/pubmed/24393429

103. Matthiesen G, Olofsson K, Rudnicki M. Ionized magnesium in Danish children with type 1 diabetes. Diabetes Care 2004, 27(3), 1216-1217. http://care.diabetesjournals.org/content/27/5/1216

104. Uğurlu V, Binay Ç, Şimşek E, Bal C. Cellular Trace Element Changes in Type 1 Diabetes Patients. J Clin Res PediatrEndocrinol. 2016 Jun 5;8(2):180-6. http://www.ncbi.nlm.nih.gov/pubmed/27086726

105. Huerta MG et al. Magnesium deficiency is associated with insulin resistance in obese children. Diabetes Care 2005; 28(5), 1175-1181. http://care.diabetesjournals.org/content/28/5/1175

106. NIH, National Institutes of Health. Selenium Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/

107. Özenç S et al. Selenium, zinc and copper levels and their relation with HbA1c status in children with type 1 diabetes mellitus. In t J Diabetes DevCtrs, 2015, 35(4) 514-518. http://link.springer.com/article/10.1007/s13410-015-0327-y

108. NIH, National Institutes of Health. Zinc Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/

109. Wu Y et al. Zinc stimulates glucose consumption by modulating the insulin signaling pathway in L6 myotubes: essential roles of Akt-GLUT4, GSK3β and mTOR-S6K1. J NutrBiochem. 2016 May 31;34:126-135. http://www.ncbi.nlm.nih.gov/pubmed/27295130

110. Jayawardena R, Ranasinghe P, Galappatthy P, Malkanthi GR, Katulanda P. Effects of zinc supplementation on diabetes mellitus: a systematic review and meta-analysis. DiabetolMetab Syndrome 2012; 4:13. https://www.ncbi.nlm.nih.gov/pubmed/22515411

111. Bideci A, Amurdan MO, Cinaz P, Dursun H, Demirel F. Serum zinc, insulin-like growth factor-I and insulin-like growth factor binding protein-3 levels in children with type 1 diabetes mellitus. J Pediatr Endocrinol Metab. 2005;18(10):1007–11. https://www.ncbi.nlm.nih.gov/pubmed/16355814

112. Angelova M, Schentov B, Nedkova V, Nikoloff G, Alexiev AI, Petrova Ch. Serum zinc in children with enterocolitis, chronic diarrhea with malabsorption syndrome and type 1 diabetes. Trakia Journal of Sciences. 2006;4:11–7

113. Tuvemo T, Ewald U, Kobbah M, Proos LA. Serum magnesium and protein concentrations during the first five years of insulin-dependent diabetes in children. Acta Paediatr. 1997;418(Suppl):7–10. https://www.ncbi.nlm.nih.gov/pubmed/9055931

114. Rohn RD, Pleban P, Jenkins LL. Magnesium, zinc and copper in plasma and blood cellular components in children with IDDM. Clin Chim Acta. 1993;215(1):21–8. https://www.ncbi.nlm.nih.gov/pubmed/8513565

115. Estakhri M et al.Serum Zinc Levels in Children and Adolescents with Type-1 Diabetes Mellitus. Iran J Public Health. 2011; 40(4): 83–88. https://www.ncbi.nlm.nih.gov/pubmed/23113106

116. Nakamura T, Higashi A, Nishiyama S, Fujimoto S Matsuda. Kinetics of Zinc Status in Children with IDDM. Diabetes Care 1991; 14(7):
553-557. https://www.ncbi.nlm.nih.gov/pubmed/1914794

117. Heneman K, Zidenberg-Cherr S. Some facts about phytochemicals. Center for Health and Nutrition Research University of California. October 2008. http://nutrition.ucdavis.edu/content/infosheets/fact-pro-phytochemical.pdf

118. Jacques PF, Cassidy A, Rogers G, Peterson JJ, Meigs JB, Dwyer JT. Higher Dietary Flavonol Intake Is Associated with Lower Incidence of Type 2 Diabetes1,2. J Nutr. 2013 Sep; 143(9): 1474–1480. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3743276/

119. Jiao H, Hu G, Gu D, Ni X. Having a promising efficacy on type II diabetes, it’s definitely a green tea time. Curr Med Chem. 2015;22(1):70-9. https://www.ncbi.nlm.nih.gov/pubmed/25139278

120. Szkudelski T, Szkudelska K.Anti-diabetic effects of resveratrol. Ann N Y Acad Sci. 2011 Jan;1215:34-9. https://www.ncbi.nlm.nih.gov/pubmed/21261639

121. Vessal M, Hemmati M, Vasei M. Antidiabetic effects of quercetin in streptozocin-induced diabetic rats. Comp BiochemPhysiol C ToxicolPharmacol. 2003 Jul;135C(3):357-64. https://www.ncbi.nlm.nih.gov/pubmed/12927910

122. Nabavi SF et al. Curcumin: a natural product for diabetes and its complications. CurrTop Med Chem. 2015;15(23):2445-55. https://www.ncbi.nlm.nih.gov/pubmed/26088351

123. Crawford P et al. Assessment of the effect of lifestyle intervention plus water-soluble cinnamon extract on lowering blood glucose in pre-diabetics, a randomized, double-blind, multicenter, placebo controlled trial: study protocol for a randomized controlled trial. Trials. 2016 Jan 5;17:9. http://www.ncbi.nlm.nih.gov/pubmed/26732017

124. Sahib AS. Anti-diabetic and antioxidant effect of cinnamon in poorly controlled type-2 diabetic Iraqi patients: A randomized, placebo-controlled clinical trial. J IntercultEthnopharmacol. 2016 Feb 21;5(2):108-13. http://www.ncbi.nlm.nih.gov/pubmed/27104030

125. Im K, Issac A, NM J, Ninan E, Maliakel B, Kuttan R.Effects of the polyphenol content on the anti-diabetic activity of Cinnamomum zeylanicum extracts. Food Funct. 2014 Sep;5(9):2208-20. http://www.ncbi.nlm.nih.gov/pubmed/25051315

126. Jiménez-Osorio AS, Monroy A, Alavez S. Curcumin and insulin resistance-Molecular targets and clinical evidences. Biofactors. 2016 Jun 21. http://www.ncbi.nlm.nih.gov/pubmed/27325504

127. Weisberg S, Leibel R, Tortoriello DV. Proteasome inhibitors, including curcumin, improve pancreatic β-cell function and insulin sensitivity in diabetic mice. Nutr Diabetes. 2016 Apr 25;6:e205. doi: 10.1038/nutd.2016.13. http://www.ncbi.nlm.nih.gov/pubmed/27110686

128. Gunnink LK et al. Curcumin directly inhibits the transport activity of GLUT1. Biochimie. 2016 Jun;125:179-85. http://www.ncbi.nlm.nih.gov/pubmed/27039889

129. Anupunpisit V, Petpiboolthai H, Khimmaktong W. Microvasculature Improvement of Heart in Diabetic Rat with Curcumin Supplementation. J Med Assoc Thai. 2015 Nov;98Suppl 10:S74-83. http://www.ncbi.nlm.nih.gov/pubmed/27276836

130. Kim BH et al. Protective Effects of Curcumin on Renal Oxidative Stress and Lipid Metabolism in a Rat Model of Type 2 Diabetic Nephropathy. Yonsei Med J. 2016 May;57(3):664-73. http://www.ncbi.nlm.nih.gov/pubmed/26996567

131. Elburki MS et al. A novel chemically modified curcumin reduces inflammation-mediated connective tissue breakdown in a rat model of diabetes: periodontal and systemic effects. J Periodontal Res. 2016 Apr 1. http://www.ncbi.nlm.nih.gov/pubmed/27038334

132. Keske MA et al. Vascular and metabolic actions of the green tea polyphenol epigallocatechingallate. Curr Med Chem. 2015;22(1):59-69. http://www.ncbi.nlm.nih.gov/pubmed/25312214

133. Borges CM, Papadimitriou A, Duarte DA, Lopes de Faria JM, Lopes de Faria JB. The use of green tea polyphenols for treating residual
albuminuria in diabetic nephropathy: A double- blind randomised clinical trial. Sci Rep. 2016 Jun 20;6:28282. http://www.ncbi.nlm.nih.gov/pubmed/27320846

134. Raposo D, Morgado C, Pereira-Terra P, Tavares I.
Nociceptive spinal cord neurons of laminae I-III exhibit oxidative stress damage during diabetic neuropathy which is prevented by early antioxidant treatment with epigallocatechin- gallate (EGCG). Brain Res Bull. 2015 Jan;110:68-75. http://www.ncbi.nlm.nih.gov/pubmed/25522867

135. Eid HM, Nachar A, Thong F, Sweeney G, Haddad
PS.The molecular basis of the antidiabetic action of quercetin in cultured skeletal muscle cells and hepatocytes. Pharmacogn Mag. 2015 Jan-Mar;11(41):74-81. http://www.ncbi.nlm.nih.gov/pubmed/25709214

136. Kitti M et al. Quercetin Stimulates Insulin Secretion and Reduces the Viability of Rat INS-1 Beta-Cells. Cell PhysiolBiochem. 2016 Jun 24;39(1):278-293. http://www.ncbi.nlm.nih.gov/pubmed/27336168

137. Yan SX, Li X, Sun CD, Chen KS. Hypoglycemic and hypolipidemic effects of quercetin and its glycosides ZhongguoZhong Yao ZaZhi. 2015 Dec;40(23):4560-7. http://www.ncbi.nlm.nih.gov/pubmed/27141664

138. Wong RH, Nealon RS, Scholey A, Howe PR. Low dose resveratrol improves cerebrovascular function in type 2 diabetes mellitus. NutrMetabCardiovasc Dis. 2016 May;26(5):393-9. http://www.ncbi.nlm.nih.gov/pubmed/27105868

139. Pektaş MB et al. Resveratrol Ameliorates the
Components of Hepatic Inflammation and Apoptosis in a Rat Model of Streptozotocin-Induced Diabetes. Drug Dev Res. 2016 Feb;77(1):12-9. http://www.ncbi.nlm.nih.gov/pubmed/26748675

140. Zeng K et al. Resveratrol Prevents Retinal Dysfunction by Regulating Glutamate Transporters, Glutamine Synthetase Expression and Activity in Diabetic Retina. Neurochem Res. 2016 May;41(5):1050-64. http://www.ncbi.nlm.nih.gov/pubmed/26677078

141. NIH, National Institutes of Health. Coenzyme Q10 in depth. https://nccih.nih.gov/health/supplements/coq10

142. Tsai HY et al. Coenzyme Q10 Attenuates High
Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase Pathways. Diabetes Res. 2016;2016:6384759. http://www.ncbi.nlm.nih.gov/pubmed/26682233

143. Menke T, Niklowitz P, Wiesel T, Andler W. Antioxidant level and redox status of coenzyme Q10 in the plasma and blood cells of children with diabetes mellitus type 1.Pediatr Diabetes. 2008; 9(6):540-5. https://www.ncbi.nlm.nih.gov/pubmed/18694454

144. USDA. U.S. Department of Agriculture. Dietary, functional and total fiber. 339-441. https://fnic.nal.usda.gov/sites/fnic.nal.usda.gov/files/uploads/339-421.pdf

145. Velázquez-López L et al. Fiber in Diet Is Associated with Improvement of Glycated Hemoglobin and Lipid Profile in Mexican Patients with Type 2 Diabetes.J Diabetes Res.2016;2016:2980406. http://www.ncbi.nlm.nih.gov/pubmed/27144178

146. Nansel TR, Lipsky LM, Liu A. Greater diet quality is associated with more optimal glycemic control in a longitudinal study of youth with type 1 diabetes. Am J ClinNutr. 2016 Jul;104(1):81-7. http://www.ncbi.nlm.nih.gov/pubmed/27194309

147. Moreno LA et al. Psyllium fibre and the metabolic control of obese children and adolescents. J PhysiolBiochem. 2003;59:235–242. https://www.ncbi.nlm.nih.gov/pubmed/15000455

148. Ventura EE et al. Dietary intake and the metabolic syndrome in overweight Latino children. J Am Diet Assoc 2008, 108, 1355-1359. https://www.ncbi.nlm.nih.gov/pubmed/18656576

149. McKeown NM, Meigis JB, Liu S, Satzman E, Wilson PW, Jacques PF. Carbohydrate nutrition, insulin resistance, and the prevalence of the metabolic syndrome in the Framingham Offspring Cohort. Diabetes Care 2004; 27, 538-546. https://www.ncbi.nlm.nih.gov/pubmed/14747241

150. Cha JC, Ivanov V, Roomi MW, Kalinovsky T, Niedzwiecki A, Rath M. Nutritional improvement of metabolic syndrome parameters in immature fructose-fed wild-type mice. Mol Med Rep. 2011 Nov- Dec;4(6):1053-9. http://www.ncbi.nlm.nih.gov/pubmed/21874237

1. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med, 2006, 3(11):e442. www.ncbi.nlm.nih.gov/pubmed/17132052

2. WHO, World Health Organization. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus. Geneva, World Health Organization, 1999.

3. Atkinson M, Eisenbarth GS, Michels AW. Type 1 diabetes. Lancet. 2014 Jan 4; 383(9911): 69–82. www.ncbi.nlm.nih.gov/pmc/articles/PMC4380133

4. Barat P. Epidemiology of type 1 diabetes in children. SoinsPediatrPueric. 2016 Jan- Feb;(288):10-2. www.ncbi.nlm.nih.gov/pubmed/26776685

5. Imkampe AK, Gulliford MC. Trends in Type 1 diabetes incidence in the UK in 0- to 14-year-olds and in 15- to 34-year-olds, 1991-2008. Diabet Med. 2011 Jul;28(7):811-4. www.ncbi.nlm.nih.gov/pubmed/21395679

6. Patterson CC, Dahlquist GG, Gyürüs E, Green A, Soltész G; EURODIAB Study Group. Incidence trends for childhood type 1 diabetes in Europe during 1989-2003 and predicted new cases 2005-20: a multicentre prospective registration study. Lancet. 2009 Jun 13;373(9680):2027-33. www.ncbi.nlm.nih.gov/pubmed/19481249/

7. Pinhas-Hamiel O Zeitler P. The global spread of type 2 diabetes mellitus in children and adolescents. J Pediatr 2005;146:693–700. www.ncbi.nlm.nih.gov/pubmed/15870677

8. Pinhas-Hamiel O, Zeitler P. Acute and chronic complications of type 2 diabetes mellitus in children and adolescents. Lancet 2007;369:1823–1831. www.ncbi.nlm.nih.gov/pubmed/17531891

9. Classen JB, Classen DC. Clustering of cases of type 1 diabetes mellitus occurring 2-4 years after vaccination is consistent with clustering after infections and progression to type 1 diabetes mellitus in autoantibody positive individuals. J PediatrEndocrinolMetab. 2003 Apr- May;16(4):495-508. www.ncbi.nlm.nih.gov/pubmed/12793601

10. Classen JB, Classen DC. Clustering of cases of insulin dependent diabetes (IDDM) occurring three years after hemophilus influenza B (HiB) immunization support causal relationship between immunization and IDDM. Autoimmunity. 2002 Jul;35(4):247-53. www.ncbi.nlm.nih.gov/pubmed/12482192

11. Al-Zubeidi H, Leon-Chi L, Newfield RS. Low vitamin D level in pediatric patients with new onset type 1 diabetes is common, especially if in ketoacidosis. Pediatr Diabetes. 2015 Dec 23. www.ncbi.nlm.nih.gov/pubmed/26694737

12. Liu C et al. Correlation of serum vitamin d level with type 1 diabetes mellitus in children: a meta- analysis. Nutr Hosp. 2015 Oct 1;32(4):1591-4. www.ncbi.nlm.nih.gov/pubmed/26545522

13. WHO, World Health Organization. What are the risk of diabetes in children? www.who.int/features/qa/65/en/

14. Copeland C, Becker D, Gottschalk M, Hale D. Type 2 Diabetes in Children and Adolescents: Risk Factors, Diagnosis, and Treatment. Clinical Diabetes 2005 Oct; 23(4): 181-185. www.clinical.diabetesjournals.org/content/23/4/181

15. Wheelock KM, Sinha M, Knowler WC, Nelson RG, Fufaa GD, Hanson RL. Metabolic Risk Factors and Type 2 Diabetes Incidence in American Indian Children J ClinEndocrinolMetab. 2016 Feb 25:jc20154309. www.ncbi.nlm.nih.gov/pubmed/26913636

16. Boulton J, Hashem KM, Jenner KH, Lloyd- Williams F, Bromley H, Capewell S. How much sugar is hidden in drinks marketed to children? A survey of fruit juices, juice drinks and smoothies. BMJ Open. 2016 Mar 23;6(3):e010330. www.ncbi.nlm.nih.gov/pubmed/27009146

17. Ma Y, He FJ, Yin Y, Hashem KM, MacGregor GA. Gradual reduction of sugar in soft drinks without substitution as a strategy to reduce overweight, obesity, and type 2 diabetes: a modelling study. Lancet Diabetes Endocrinol. 2016 Feb;4(2):105-14. www.ncbi.nlm.nih.gov/pubmed/26777597

18. Johnson RJ, Segal MS, Sautin Y. Potential role of sugar (fructose) in the epidemic of hypertension, obesity and the metabolic syndrome, diabetes, kidney disease, and cardiovascular disease. Am J ClinNutr 2007;86(4):899–906. www.ncbi.nlm.nih.gov/pubmed/17921363

19. Segal MS, Gollub E, Johnson RJ. Is the fructose index more relevant with regards to cardiovascular disease than the glycemic index? Eur J Nutr 2007;46(7):406–17. www.ncbi.nlm.nih.gov/pubmed/17763967

20. Nakagawa T et al. A causal role for uric acid in fructose-induced metabolic syndrome. Am J Physiol 2006;290(3): F625–31. www.ncbi.nlm.nih.gov/pubmed/16234313

21. WHO, Word Health Organization European Region. Data and statistics. www.euro.who.int/en/health-topics/noncommunicable-diseases/obesity/data-and-statistics

22. WHO, World Health Organization. Physical activity. www.who.int/mediacentre/factsheets/fs385/en/

23. Fernandes RA, Zanesco A. Early sport practice is related to lower prevalence of cardiovascular and metabolic outcomes in adults independently of overweight and current physical activity. Medicina (Kaunas). 2015;51(6):336-42. www.ncbi.nlm.nih.gov/pubmed/26739675

24. Huus K, Åkerman L, Raustorp A, Ludvigsson J. Physical Activity, Blood Glucose and C-Peptide in Healthy School-Children, a Longitudinal Study. PLoS One. 2016 Jun 7;11(6):e0156401. www.ncbi.nlm.nih.gov/pubmed/27270732

25. Rath M. Why animals don´t get heart attack but people do! Chapter 7: Diabetes, 2003.

26. Chrysis D, Efthymiadou A, Mermigka A, Kritikou D, Spiliotis BE. Osteoprotegerin, RANKL, ADMA, and Fetuin-A serum levels in children with
type I diabetes mellitus. Pediatr Diabetes. 2016 Mar 29. www.ncbi.nlm.nih.gov/pubmed/27028343

27. Song SH, Hardisty CA. Early-Onset Type 2
Diabetes Mellitus: An Increasing Phenomenon of Elevated Cardiovascular Risk. Expert Rev CardiovascTher. 2008;6(3):315-322. www.medscape.com/viewarticle/573459

28. al-Naama LM, Kadhim M, al-Aboud MS. Lipid profile in children with insulin dependent diabetes mellitus. J Pak Med Assoc. 2002
Jan;52(1):29-34. www.ncbi.nlm.nih.gov/pubmed/11963582

29. Petitti DB et al. Serum lipids and glucose control: the SEARCH for Diabetes in Youth study. Arch PediatrAdolesc Med. 2007 Feb;161(2):159-65. www.ncbi.nlm.nih.gov/pubmed/17283301

30. Reinehr T et al. Inflammatory Markers in Obese Adolescents with Type 2 Diabetes and Their Relationship to Hepatokines and Adipokines.J Pediatr. 2016 Mar 17. www.ncbi.nlm.nih.gov/pubmed/26996723

31. Freemark M, Levitsky L. Screening for Celiac Disease in Children with Type 1 Diabetes. Diabetes Care 2003 Jun; 26(6): 1932-1939. http://care.diabetesjournals.org/content/26/6/1932

32. Kordonouri O, Hartmann R, Deiss D, Wilms M, Gruters-Kieslich A. Natural course of autoimmune thyroiditis in type 1 diabetes: association with gender, age, diabetes duration, and puberty. Arch Dis Child. 2005 Apr; 90(4): 411–414. www.ncbi.nlm.nih.gov/pmc/articles/PMC1720371/

33. Lu MC, Chang SC, Huang KY, Koo M, Lai NS.
Higher Risk of Thyroid Disorders in Young Patients with Type 1 Diabetes: A 12-Year Nationwide, Population-Based, Retrospective Cohort Study. PLoS One. 2016 Mar
23;11(3):e0152168. www.ncbi.nlm.nih.gov/pubmed/27007574

34. Litmanovitch E, Geva R, Rachmiel R. Short and long term neuro-behavioral alterations in type 1 diabetes mellitus pediatric population. World J Diabetes. 2015 Mar 15; 6(2): 259–270. www.ncbi.nlm.nih.gov/pmc/articles/PMC4360419/

35. Jabbour G, Henderson M, Mathieu ME. Barriers to Active Lifestyles in Children with Type 1 Diabetes. Can J Diabetes. 2016 Apr;40(2):170-2. www.ncbi.nlm.nih.gov/pubmed/27038139

36. Brady CC et al. Obese adolescents with type 2 diabetes perform worse than controls on cognitive and behavioral assessments. Pediatr Diabetes. 2016 Mar 29. www.ncbi.nlm.nih.gov/pubmed/27028236

37. Suh JS et al.Urinary markers in the early stage of nephropathy in patients with childhood-onset type 1 diabetes. PediatrNephrol. 2016 31(4):623-31. www.ncbi.nlm.nih.gov/pubmed/26525196

38. Papadopoulou-Marketou N et al.NGAL and cystatin C: two possible early markers of diabetic nephropathy in young patients with type 1 diabetes mellitus: one year follow up. Hormones (Athens). 2015 Apr-Jun;14(2):232-40. www.ncbi.nlm.nih.gov/pubmed/25402375

39. Craig EM, Craig J, DabeleaD,Balde N, Seth A, Donaghue KC. ISPAD Clinical Practice Consensus Guidelines 2014 Compendium. Definition, epidemiology, and classification of diabetes in children and adolescents. http://onlinelibrary.wiley.com/doi/10.1111/pedi.12186/abstract

40. Li L, Jick S, Breitenstein S, Michel A. Prevalence of Diabetes and Diabetic Nephropathy in a Large U.S. Commercially Insured Pediatric Population,
2002–2013. Diabetes Care 2016 Feb; 39(2):278-284. http://care.diabetesjournals.org/content/39/2/278

41. Trotta D, Verrotti A, Salladini C, Chiarelli F.
Diabetic neuropathy in children and adolescents. Pediatr Diabetes. 2004 Mar;5(1):44-57. http://www.ncbi.nlm.nih.gov/pubmed/15043690

42. Hamid A, Wharton HM, Mills A, Gibson JM, Clarke M, Dodson PM. Diagnosis of retinopathy in children younger than 12 years of age: implications for the diabetic eye screening guidelines in the UK. Eye (Lond). 2016 Apr 15. http://www.ncbi.nlm.nih.gov/pubmed/27080488

43. Hermann G et al. Comorbidity of Type 1 Diabetes and Juvenile Idiopathic Arthritis. April 2015 Volume 166, Issue 4, Pages 930–935.e3. http://www.jpeds.com/article/S0022-3476(14)01195-0/fulltext

44. Mantravadi M. Pediatric Osteoporosis, 2016. http://emedicine.medscape.com/article/985221-overview#a3

45. Lalla E et al. Periodontal Changes in Children and Adolescents With Diabetes. Diabetes Care 2006 Feb; 29(2): 295-299. http://care.diabetesjournals.org/content/29/2/295

46. Xavier AC, Silva IN, Costa Fde O, Corrêa DS. Periodontal status in children and adolescents with type 1 diabetes mellitus. Arq Bras EndocrinolMetabol. 2009 Apr;53(3):348-54. http://www.ncbi.nlm.nih.gov/pubmed/19578597

47. American Diabetes Association. Skin Complications. www.diabetes.org/living-with-diabetes/complications/skin-complications

48. Kowalewska B, Kawko M, Zorena K, Myśliwiec M. Yeast-like fungi in the gastrointestinal tract in children and adolescents with diabetes type 1. PediatrEndocrinol Diabetes Metab. 2015;20(4):170-7. http://www.ncbi.nlm.nih.gov/pubmed/26615584

49. Kowalewska B, Zorena K, Szmigiero-Kawko M, Wąż P, Myśliwiec M. Higher diversity in fungal species discriminates children with type 1 diabetes mellitus from healthy control. Patients Prefer Adherence. 2016; 10:591-599. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4844445/

50. FDA, Food and Drug administration. Code of Federal Regulation. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=310.517

51. Onge ES, Miller SA, Motycka C, DeBerry A. A review of the treatment of type 2 diabetes in children. J PediatrPharmacolTher. 2015 Jan-Feb;20(1):4-16. http://www.ncbi.nlm.nih.gov/pubmed/25859165

52. Cherubini V, Pintaudi B, Iannilli A, Pambianchi M, Ferrito L, Nicolucci A. Long-acting Insulin Analogs Effect on gh/igf Axis of Children with Type 1 Diabetes: a Randomized, Open-label, Two-period, Cross-over Trial. ExpClinEndocrinol Diabetes. 2016 Mar 29. http://www.ncbi.nlm.nih.gov/pubmed/27023008

53. Cope JU, Samuels-Reid JH, Morrison AE. Pediatric Use of Insulin Pump Technology: A Retrospective Study of Adverse Events in Children Ages 1–12 Years J Diabetes Sci Technol.2012 Sep; 6(5): 1053–1059. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570839/

54. Gao YQ , Gao M, Xue Y. Treatment of diabetes in children. ExpTher Med. 2016 Apr;11(4):1168-1172 http://www.ncbi.nlm.nih.gov/pubmed/27073417

55. Libman IM et al. Effect of Metformin Added to Insulin on Glycemic Control Among Overweight/ Obese Adolescents With Type 1 Diabetes: A Randomized Clinical Trial. JAMA. 2015 Dec 1;314(21):2241-50. http://www.ncbi.nlm.nih.gov/pubmed/26624824

56. Lysy J, Israeli E, Goldin E. The prevalence of chronic diarrhea among diabetic patients. Am J Gastroenterol. 1999 Aug;94(8):2165-70.

57. Pozzo AM. Pediatric Type 2 Diabetes Mellitus Medication. Medscape, May 2014. http://reference.medscape.com/article/925700-medication

58. Wen YW, Tsai YW, Huang WF, Hsiao FY, Chen PF.The potentially inappropriate prescription of new drug: thiazolidinediones for patients with type II diabetes in Taiwan. Pharmacoepidemiol Drug Saf. 2011 Jan;20(1):20-9. http://www.ncbi.nlm.nih.gov/pubmed/21182151

59. Ahuja V, Chou CH. Novel Therapeutics for Diabetes: Uptake, Usage Trends, and Comparative Effectiveness. CurrDiab Rep. 2016 Jun;16(6):47. http://www.ncbi.nlm.nih.gov/pubmed/27076180

60. Onge ES, Miller SA, Motycka C, DeBerry A. A review of the treatment of type 2 diabetes in children. J PediatrPharmacolTher. 2015 Jan-Feb;20(1):4-16. http://www.ncbi.nlm.nih.gov/pubmed/25859165

61. FDA, Food and Drug administration. Code of Federal Regulation. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=310.517

62. Yaffe S. Rational Therapeutics for Infants and Children: Workshop Summary. Similarities and Dissimilarities in Physiology, Metabolism, and Disease States and Responses to Therapy in Children and Adults. National Academies Press (US); 2000.

63. Hines RN. Ontogeny of human hepatic cytochromes P450. J BiochemMolToxicol 21:169–175, 2007. http://onlinelibrary.wiley.com/doi/10.1002/jbt.20179/abstract

64. Sahota PS, Popp JA, Hardisty JF, Gopinath G. Toxicologic pathology non clinical safety assessment. Exocrine pancreas. 2013 CRC Press, Taylor & Francis Group.

65. Ulrich AB, Standop J, Schmied BM, Schneider MB, Lawson TA, Pour PM. Species Differences in the Distribution of Drug-Metabolizing Enzymes in the Pancreas. Toxicologic Pathology, vol 30, no 2, pp 247–253, 2002. http://tpx.sagepub.com/content/30/2/247

66. WHO, World Health Organization.Micronutrients.
http://www.who.int/nutrition/topics/micronutrients/en/

67. Dr. Rath Research Institute www.drrathresearch.org

68. NIH, National Institutes of Health. Vitamin A Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/VitaminA-HealthProfessional/

69. Meerza D, Iqbal S, Zaheer S, Naseem I. Retinoids have therapeutic action in type 2 diabetes. Nutrition 2016 Jul-Aug;32(7-8):898-903. http://www.ncbi.nlm.nih.gov/pubmed/27134203

70. Iqbal S, Naseem I. Role of vitamin A in type 2 diabetes mellitus biology: Effects of intervention therapy in a deficient state. Nutrition. July– August, 2015 Volume 31, Issues 7-8, Pages 901–907. http://www.nutritionjrnl.com/article/S0899-9007(14)00552-8/fulltext

71. Trasino SE, Benoit DY, Gudas LJ. Vitamin A Deficiency Causes Hyperglycemia and Loss of Pancreatic β-Cell Mass. J BiolChemistry. 2015, 290(3), 1456-1473. http://www.ncbi.nlm.nih.gov/pubmed/25451926

72. NIH, National Institutes of Health. Vitamin B12 Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/

73. Kibirige D, Mwebaze R. Vitamin B12 deficiency among patients with diabetes mellitus: is routine screening and supplementation justified? J. DiabMetab Disorders 2013; 12:7. https://jdmdonline.biomedcentral.com/articles/10.1186/2251-6581-12-17

74. Ho M et al. Vitamin B12 in obese adolescents with clinical features of insulin resistance. Nutrients. 2014 Dec 4;6(12):5611-8. https://www.ncbi.nlm.nih.gov/pubmed/25486369

75. Damião CP et al. Prevalence of vitamin B12 deficiency in type 2 diabetic patients using metformin: a cross-sectional study. Sao Paulo Med J. 2016 Jun 3. http://www.ncbi.nlm.nih.gov/pubmed/27276084

76. Akinlade KS, Agbebaku SO, Rahamon SK, Balogun WO. Vitamin B12 levels in patients with type 2 diabetes mellitus on metformin. Ann IbPostgrad Med. 2015 Dec;13(2):79-83. http://www.ncbi.nlm.nih.gov/pubmed/27162518

77. Dekelbab B, Kakkannat A. Prevalence of Vitamin B12 Deficiency in Children and Adolescents Treated with Metformin. Endocrine Society’s
96th Annual Meeting and Expo, June 21–24, 2014 – Chicago.

78. NIH, National Institutes of Health. Vitamin C Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/VitaminC-HealthProfessional/#h2

79. Tu H et al. Low Red Blood Cell Vitamin C Concentrations Induce Red Blood Cell Fragility: A Link to Diabetes Via Glucose, Glucose Transporters, and Dehydroascorbic Acid. EBioMedicine. 2015 Oct 3;2(11):1735-50. http://www.ncbi.nlm.nih.gov/pubmed/26870799

80. Li L, Jick S, Breitenstein S, Michel A. Prevalence of Diabetes and Diabetic Nephropathy in a Large U.S. Commercially Insured Pediatric Population,
2002–2013. Diabetes Care 2016 Feb; 39(2): 278-284. http://care.diabetesjournals.org/content/39/2/278

81. Christie-David DJ, Girgis CM, Gunton JE.
Effects of vitamin C and D in type 2 diabetes mellitus, Nutr and Dietary Suppl 2015, 15(7), 21-28. www.researchgate.net/publication/272092706_Effects_of_vitamins_C_and_D_in_type_2_diabetes_mellitus

82. Chou ST, Tseng ST. Oxidative stress markers in type 2 diabetes patients with diabetic nephropathy. ClinExpNephrol. 2016 May 27. http://www.ncbi.nlm.nih.gov/pubmed/27233502

83. ArdekaniMA ,Ardekani AS. Effect of vitamin C on blood glucose, serum lipids & serum insulin in type II diabetes patients. Indian J Med Research, vol. 126, no. 5, pp. 471–474, 2007. http://www.ncbi.nlm.nih.gov/pubmed/18160753

84. Donin AS et al. Fruit, vegetable and vitamin C intakes and plasma vitamin C: cross-sectional associations with insulin resistance and glycaemia in 9-10 year-old children. Diabet Med. 2016 Mar;33(3):307-15. http://www.ncbi.nlm.nih.gov/pubmed/26498636

85. NIH, National Institutes of Health. Vitamin D Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/

86. Mosso C, Hodgson MI, Ortiz T, Reyes ML.
Bone mineral density in young Chilean patients with type 1 diabetes mellitus. J PediatrEndocrinolMetab. 2016 Jun 1;29(6):731-6. http://www.ncbi.nlm.nih.gov/pubmed/27054593

87. Al Sawah S, Compher CW, Hanlon AL, Lipman TH. 25-Hydroxyvitamin D and glycemic control: A cross-sectional study of children and adolescents with type 1 diabetes. Diabetes Res ClinPract. 2016 May;115:54-9. http://www.ncbi.nlm.nih.gov/pubmed/27242123

88. Mohammadian S, Fatahi N, Zaeri H, Ali Vakili M. Effect of Vitamin D3 supplement in glycemic control of pediatrics with type 1 diabetes mellitus and vitamin D deficiency.J Clin Diagn Res 2015, 9(3), SC05-SC07. https://www.ncbi.nlm.nih.gov/pubmed/25954674

89. He R et al. Vitamin D deficiency increases the risk of peripheral neuropathy in Chinese patients with Type 2 diabetes. Diabetes Metab Res Rev. 2016 May 7. http://www.ncbi.nlm.nih.gov/pubmed/27155442

90. Kaur H et al. Vitamin D deficiency is associated with retinopathy in children and adolescents with type 1 diabetes. Diabetes Care. 2011 Jun;34(6):1400-2. https://www.ncbi.nlm.nih.gov/pubmed/21515836

91. NIH, National Institutes of Health. Vitamin K Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/VitaminK-HealthProfessional/#h3

92. Choi HJ et al. Vitamin K2 supplementation improves insulin sensitivity via osteocalcin metabolism: a placebo-controlled trial. Diabetes Care. 2011 Sep;34(9):e147. https://www.ncbi.nlm.nih.gov/pubmed/21868771

93. Manna P, Kalita J. Beneficial role of vitamin K supplementation on insulin sensitivity, glucose metabolism, and the reduced risk of type 2 diabetes: A review. Nutrition. 2016 Jul-Aug;32(7-8):732-9. http://www.ncbi.nlm.nih.gov/pubmed/27133809

94. DiNicolantonio JJ, Bhutani J, O’Keefe JH. The health benefits of vitamin K. Open Heart. 2015 Oct 6;2(1):e000300. http://www.ncbi.nlm.nih.gov/pubmed/26468402

95. NIH, National Institutes of Health. Chromium Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/Chromium-HealthProfessional/

96. Karagun BS et al.Chromium levels in healthy and newly diagnosed type 1 diabetic children. Pediatr Int. 2012 54(6):780-785. https://www.ncbi.nlm.nih.gov/pubmed/22783884

97. McIver DJ, Grizales AM, Brownstein JS, Goldfine AB. Risk of Type 2 Diabetes Is Lower in US Adults Taking Chromium-Containing Supplements. J Nutr. 2015 Dec;145(12):2675-82. http://www.ncbi.nlm.nih.gov/pubmed/26446484

98. NIH, National Institutes of Health. Iron Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/Iron-HealthProfessional/

99. Mojs E, Stanisławska-Kubiak M, Wójciak RW, Wojciechowska J, Przewoźniak S. Reduced iron parameters and cognitive processes in children and adolescents with DM1 compared to those with standard parameters. J Investig Med. 2016 Mar;64(3):782-5. http://www.ncbi.nlm.nih.gov/pubmed/26912011

100. NIH, National Institutes of Health. Magnesium Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/

101. Lin CC, Tsweng GJ, Lee CF, Chen BH, Huang YL. Magnesium, zinc, and chromium levels in children, adolescents, and young adults with type 1 diabetes. Clin. Nutr2016; 35, 880-884. https://www.ncbi.nlm.nih.gov/pubmed/26096861

102. Galli-Tsinopoulou A et al. Association between magnesium concentration and HbA1c in children and adolescents with type 1 diabetes mellitus. J Diabetes, 2014; 6(4), 369-377. https://www.ncbi.nlm.nih.gov/pubmed/24393429

103. Matthiesen G, Olofsson K, Rudnicki M. Ionized magnesium in Danish children with type 1 diabetes. Diabetes Care 2004, 27(3), 1216-1217. http://care.diabetesjournals.org/content/27/5/1216

104. Uğurlu V, Binay Ç, Şimşek E, Bal C. Cellular Trace Element Changes in Type 1 Diabetes Patients. J Clin Res PediatrEndocrinol. 2016 Jun 5;8(2):180-6. http://www.ncbi.nlm.nih.gov/pubmed/27086726

105. Huerta MG et al. Magnesium deficiency is associated with insulin resistance in obese children. Diabetes Care 2005; 28(5), 1175-1181. http://care.diabetesjournals.org/content/28/5/1175

106. NIH, National Institutes of Health. Selenium Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/

107. Özenç S et al. Selenium, zinc and copper levels and their relation with HbA1c status in children with type 1 diabetes mellitus. In t J Diabetes DevCtrs, 2015, 35(4) 514-518. http://link.springer.com/article/10.1007/s13410-015-0327-y

108. NIH, National Institutes of Health. Zinc Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/

109. Wu Y et al. Zinc stimulates glucose consumption by modulating the insulin signaling pathway in L6 myotubes: essential roles of Akt-GLUT4, GSK3β and mTOR-S6K1. J NutrBiochem. 2016 May 31;34:126-135. http://www.ncbi.nlm.nih.gov/pubmed/27295130

110. Jayawardena R, Ranasinghe P, Galappatthy P, Malkanthi GR, Katulanda P. Effects of zinc supplementation on diabetes mellitus: a systematic review and meta-analysis. DiabetolMetab Syndrome 2012; 4:13. https://www.ncbi.nlm.nih.gov/pubmed/22515411

111. Bideci A, Amurdan MO, Cinaz P, Dursun H, Demirel F. Serum zinc, insulin-like growth factor-I and insulin-like growth factor binding protein-3 levels in children with type 1 diabetes mellitus. J Pediatr Endocrinol Metab. 2005;18(10):1007–11. https://www.ncbi.nlm.nih.gov/pubmed/16355814

112. Angelova M, Schentov B, Nedkova V, Nikoloff G, Alexiev AI, Petrova Ch. Serum zinc in children with enterocolitis, chronic diarrhea with malabsorption syndrome and type 1 diabetes. Trakia Journal of Sciences. 2006;4:11–7

113. Tuvemo T, Ewald U, Kobbah M, Proos LA. Serum magnesium and protein concentrations during the first five years of insulin-dependent diabetes in children. Acta Paediatr. 1997;418(Suppl):7–10. https://www.ncbi.nlm.nih.gov/pubmed/9055931

114. Rohn RD, Pleban P, Jenkins LL. Magnesium, zinc and copper in plasma and blood cellular components in children with IDDM. Clin Chim Acta. 1993;215(1):21–8. https://www.ncbi.nlm.nih.gov/pubmed/8513565

115. Estakhri M et al.Serum Zinc Levels in Children and Adolescents with Type-1 Diabetes Mellitus. Iran J Public Health. 2011; 40(4): 83–88. https://www.ncbi.nlm.nih.gov/pubmed/23113106

116. Nakamura T, Higashi A, Nishiyama S, Fujimoto S Matsuda. Kinetics of Zinc Status in Children with IDDM. Diabetes Care 1991; 14(7):
553-557. https://www.ncbi.nlm.nih.gov/pubmed/1914794

117. Heneman K, Zidenberg-Cherr S. Some facts about phytochemicals. Center for Health and Nutrition Research University of California. October 2008. http://nutrition.ucdavis.edu/content/infosheets/fact-pro-phytochemical.pdf

118. Jacques PF, Cassidy A, Rogers G, Peterson JJ, Meigs JB, Dwyer JT. Higher Dietary Flavonol Intake Is Associated with Lower Incidence of Type 2 Diabetes1,2. J Nutr. 2013 Sep; 143(9): 1474–1480. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3743276/

119. Jiao H, Hu G, Gu D, Ni X. Having a promising efficacy on type II diabetes, it’s definitely a green tea time. Curr Med Chem. 2015;22(1):70-9. https://www.ncbi.nlm.nih.gov/pubmed/25139278

120. Szkudelski T, Szkudelska K.Anti-diabetic effects of resveratrol. Ann N Y Acad Sci. 2011 Jan;1215:34-9. https://www.ncbi.nlm.nih.gov/pubmed/21261639

121. Vessal M, Hemmati M, Vasei M. Antidiabetic effects of quercetin in streptozocin-induced diabetic rats. Comp BiochemPhysiol C ToxicolPharmacol. 2003 Jul;135C(3):357-64. https://www.ncbi.nlm.nih.gov/pubmed/12927910

122. Nabavi SF et al. Curcumin: a natural product for diabetes and its complications. CurrTop Med Chem. 2015;15(23):2445-55. https://www.ncbi.nlm.nih.gov/pubmed/26088351

123. Crawford P et al. Assessment of the effect of lifestyle intervention plus water-soluble cinnamon extract on lowering blood glucose in pre-diabetics, a randomized, double-blind, multicenter, placebo controlled trial: study protocol for a randomized controlled trial. Trials. 2016 Jan 5;17:9. http://www.ncbi.nlm.nih.gov/pubmed/26732017

124. Sahib AS. Anti-diabetic and antioxidant effect of cinnamon in poorly controlled type-2 diabetic Iraqi patients: A randomized, placebo-controlled clinical trial. J IntercultEthnopharmacol. 2016 Feb 21;5(2):108-13. http://www.ncbi.nlm.nih.gov/pubmed/27104030

125. Im K, Issac A, NM J, Ninan E, Maliakel B, Kuttan R.Effects of the polyphenol content on the anti-diabetic activity of Cinnamomum zeylanicum extracts. Food Funct. 2014 Sep;5(9):2208-20. http://www.ncbi.nlm.nih.gov/pubmed/25051315

126. Jiménez-Osorio AS, Monroy A, Alavez S. Curcumin and insulin resistance-Molecular targets and clinical evidences. Biofactors. 2016 Jun 21. http://www.ncbi.nlm.nih.gov/pubmed/27325504

127. Weisberg S, Leibel R, Tortoriello DV. Proteasome inhibitors, including curcumin, improve pancreatic β-cell function and insulin sensitivity in diabetic mice. Nutr Diabetes. 2016 Apr 25;6:e205. doi: 10.1038/nutd.2016.13. http://www.ncbi.nlm.nih.gov/pubmed/27110686

128. Gunnink LK et al. Curcumin directly inhibits the transport activity of GLUT1. Biochimie. 2016 Jun;125:179-85. http://www.ncbi.nlm.nih.gov/pubmed/27039889

129. Anupunpisit V, Petpiboolthai H, Khimmaktong W. Microvasculature Improvement of Heart in Diabetic Rat with Curcumin Supplementation. J Med Assoc Thai. 2015 Nov;98Suppl 10:S74-83. http://www.ncbi.nlm.nih.gov/pubmed/27276836

130. Kim BH et al. Protective Effects of Curcumin on Renal Oxidative Stress and Lipid Metabolism in a Rat Model of Type 2 Diabetic Nephropathy. Yonsei Med J. 2016 May;57(3):664-73. http://www.ncbi.nlm.nih.gov/pubmed/26996567

131. Elburki MS et al. A novel chemically modified curcumin reduces inflammation-mediated connective tissue breakdown in a rat model of diabetes: periodontal and systemic effects. J Periodontal Res. 2016 Apr 1. http://www.ncbi.nlm.nih.gov/pubmed/27038334

132. Keske MA et al. Vascular and metabolic actions of the green tea polyphenol epigallocatechingallate. Curr Med Chem. 2015;22(1):59-69. http://www.ncbi.nlm.nih.gov/pubmed/25312214

133. Borges CM, Papadimitriou A, Duarte DA, Lopes de Faria JM, Lopes de Faria JB. The use of green tea polyphenols for treating residual
albuminuria in diabetic nephropathy: A double- blind randomised clinical trial. Sci Rep. 2016 Jun 20;6:28282. http://www.ncbi.nlm.nih.gov/pubmed/27320846

134. Raposo D, Morgado C, Pereira-Terra P, Tavares I.
Nociceptive spinal cord neurons of laminae I-III exhibit oxidative stress damage during diabetic neuropathy which is prevented by early antioxidant treatment with epigallocatechin- gallate (EGCG). Brain Res Bull. 2015 Jan;110:68-75. http://www.ncbi.nlm.nih.gov/pubmed/25522867

135. Eid HM, Nachar A, Thong F, Sweeney G, Haddad
PS.The molecular basis of the antidiabetic action of quercetin in cultured skeletal muscle cells and hepatocytes. Pharmacogn Mag. 2015 Jan-Mar;11(41):74-81. http://www.ncbi.nlm.nih.gov/pubmed/25709214

136. Kitti M et al. Quercetin Stimulates Insulin Secretion and Reduces the Viability of Rat INS-1 Beta-Cells. Cell PhysiolBiochem. 2016 Jun 24;39(1):278-293. http://www.ncbi.nlm.nih.gov/pubmed/27336168

137. Yan SX, Li X, Sun CD, Chen KS. Hypoglycemic and hypolipidemic effects of quercetin and its glycosides ZhongguoZhong Yao ZaZhi. 2015 Dec;40(23):4560-7. http://www.ncbi.nlm.nih.gov/pubmed/27141664

138. Wong RH, Nealon RS, Scholey A, Howe PR. Low dose resveratrol improves cerebrovascular function in type 2 diabetes mellitus. NutrMetabCardiovasc Dis. 2016 May;26(5):393-9. http://www.ncbi.nlm.nih.gov/pubmed/27105868

139. Pektaş MB et al. Resveratrol Ameliorates the
Components of Hepatic Inflammation and Apoptosis in a Rat Model of Streptozotocin-Induced Diabetes. Drug Dev Res. 2016 Feb;77(1):12-9. http://www.ncbi.nlm.nih.gov/pubmed/26748675

140. Zeng K et al. Resveratrol Prevents Retinal Dysfunction by Regulating Glutamate Transporters, Glutamine Synthetase Expression and Activity in Diabetic Retina. Neurochem Res. 2016 May;41(5):1050-64. http://www.ncbi.nlm.nih.gov/pubmed/26677078

141. NIH, National Institutes of Health. Coenzyme Q10 in depth. https://nccih.nih.gov/health/supplements/coq10

142. Tsai HY et al. Coenzyme Q10 Attenuates High
Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase Pathways. Diabetes Res. 2016;2016:6384759. http://www.ncbi.nlm.nih.gov/pubmed/26682233

143. Menke T, Niklowitz P, Wiesel T, Andler W. Antioxidant level and redox status of coenzyme Q10 in the plasma and blood cells of children with diabetes mellitus type 1.Pediatr Diabetes. 2008; 9(6):540-5. https://www.ncbi.nlm.nih.gov/pubmed/18694454

144. USDA. U.S. Department of Agriculture. Dietary, functional and total fiber. 339-441. https://fnic.nal.usda.gov/sites/fnic.nal.usda.gov/files/uploads/339-421.pdf

145. Velázquez-López L et al. Fiber in Diet Is Associated with Improvement of Glycated Hemoglobin and Lipid Profile in Mexican Patients with Type 2 Diabetes.J Diabetes Res.2016;2016:2980406. http://www.ncbi.nlm.nih.gov/pubmed/27144178

146. Nansel TR, Lipsky LM, Liu A. Greater diet quality is associated with more optimal glycemic control in a longitudinal study of youth with type 1 diabetes. Am J ClinNutr. 2016 Jul;104(1):81-7. http://www.ncbi.nlm.nih.gov/pubmed/27194309

147. Moreno LA et al. Psyllium fibre and the metabolic control of obese children and adolescents. J PhysiolBiochem. 2003;59:235–242. https://www.ncbi.nlm.nih.gov/pubmed/15000455

148. Ventura EE et al. Dietary intake and the metabolic syndrome in overweight Latino children. J Am Diet Assoc 2008, 108, 1355-1359. https://www.ncbi.nlm.nih.gov/pubmed/18656576

149. McKeown NM, Meigis JB, Liu S, Satzman E, Wilson PW, Jacques PF. Carbohydrate nutrition, insulin resistance, and the prevalence of the metabolic syndrome in the Framingham Offspring Cohort. Diabetes Care 2004; 27, 538-546. https://www.ncbi.nlm.nih.gov/pubmed/14747241

150. Cha JC, Ivanov V, Roomi MW, Kalinovsky T, Niedzwiecki A, Rath M. Nutritional improvement of metabolic syndrome parameters in immature fructose-fed wild-type mice. Mol Med Rep. 2011 Nov- Dec;4(6):1053-9. http://www.ncbi.nlm.nih.gov/pubmed/21874237