Vitamin D functions are not limited to skeletal health benefits and may extend to preservation of insulin secretion and insulin sensitivity. This review summarizes the literature related to potential vitamin D influences on glucose homeostasis and insulin sensitivity. Cross-sectional data provide some evidence that circulating 25-hydroxyvitamin D (25(OH)D) is inversely associated with insulin resistance, although direct measurements of insulin sensitivity are required for confirmation. Reported associations with insulin secretion, however, are contradictory. Available prospective studies support a protective influence of high 25(OH)D concentrations on type 2 diabetes mellitus risk. There is a general lack of consistency in vitamin D intervention outcomes on insulin secretion and sensitivity, likely due to differences in subject populations, length of interventions, and forms of vitamin D supplementation. Vitamin D receptor gene polymorphisms and vitamin D interactions with the insulin like growth factor system may further influence glucose homeostasis. The ambiguity of optimal vitamin D dosing regimens and optimal therapeutic concentrations of serum 25(OH)D limit available intervention studies. Future studies, including cross-sectional and prospective, should be performed in populations at high risk for both vitamin D deficiency and type 2 diabetes mellitus. Well-designed, placebo-controlled, randomized intervention studies are required to establish a true protective influence of vitamin D on glucose homeostasis.

The gut microbiota (GM), comprising trillions of microorganisms in the gastrointestinal tract, is a key player in the development of obesity and related metabolic disorders, such as type 2 diabetes (T2D), metabolic syndrome (MS), and cardiovascular diseases. This mini-review delves into the intricate roles and mechanisms of the GM in these conditions, offering insights into potential therapeutic strategies targeting the microbiota. The review elucidates the diversity and development of the human GM, highlighting its pivotal functions in host physiology, including nutrient absorption, immune regulation, and energy metabolism. Studies show that GM dysbiosis is linked to increased energy extraction, altered metabolic pathways, and inflammation, contributing to obesity, MS, and T2D. The interplay between dietary habits and GM composition is explored, underscoring the influence of diet on microbial diversity and metabolic functions. Additionally, the review addresses the impact of common medications and therapeutic interventions like fecal microbiota transplantation on GM composition. The evidence so far advocates for further research to delineate the therapeutic potential of GM modulation in mitigating obesity and metabolic diseases, emphasizing the necessity of clinical trials to establish effective and sustainable treatment protocols.

Background: The prevalence of type 2 diabetes (DM) in children is disturbingly increasing in parallel with the increasing childhood obesity. Better knowledge regarding the pathophysiology of type 2 DM in children is paramount to devise an effective management plan. Objective: Discuss the pathophysiology of type 2 DM in children and adolescents. Methods and Results: This is a comprehensive review of the literature on this topic. Type 2 DM in childhood is viewed as a continuum of insulin resistance (IR) which is determined by an underlying genetic predisposition, intrauterine environment, excessive food consumption, continued rapid weight gain, and poor lifestyle. Besides IR, this is compounded by multiple metabolic defects including β-cell dysfunction and inadequate insulin secretion, α-cell dysfunction, hyperglucagonemia and increased hepatic glucose production, lipotoxicity, inflammation, deficiencies in incretin production and action, and increased renal glucose reabsorption. The confluence of genetic and environmental factors underscores the complexity in disease progression. Conclusion: A consistent single risk factor for type 2 DM is obesity and related IR and therefore it is essential to curtail the progression of obesity. It is important to investigate the role of stringent dietary and nutritional approaches, medications that enhance β-cell function and insulin sensitivity.

Circulating FGF21 levels are commonly elevated in disease states. There is limited information regarding concentrations of circulating FGF21 in the absence of disease, as well as age-related differences in body composition that may contribute to FGF21 regulation across groups. The objectives of this study were to assess FGF21 levels across age groups (childhood to elder adulthood), and investigate whether body composition indices are associated with age-related differences in circulating FGF21. We cross-sectionally analyzed serum concentrations of FGF21 in 184 healthy subjects aged 5–80 y (45% male). Multiple linear regression was performed to assess the independent association of categorical age (children: 5–12 y, young adults: 20–29 y, adults: 30–50 y, older adults: 55–64 y, elder adults: 65–80 y) with FGF21 concentration taking into account DXA-measured body composition indices [bone mineral density (BMD) and percent lean, trunk, and fat mass]. We also stratified analysis by tertile of FGF21. Incremental increases in FGF21 levels were observed across age groups (youngest to highest). Age group was positively associated with FGF21 level independent of body composition indices (age group variable: β = 0.25, 0.24, 0.24, 0.23, all P < 0.0001, controlling for percent lean, BMD, percent fat, and percent trunk fat, respectively). By FGF21 tertile, age group was associated with FGF21 in the lowest tertile only (β = 13.1, 0.19, 0.18, all P ≤ 0.01, accounting for percent lean, fat and trunk fat, respectively), but not when accounting for BMD. Our findings in a healthy population display an age-related increase in serum FGF21, highlighting a potential age effect in response to metabolic demand over the lifecourse. FGF21 levels increase with age independently of body composition. At lower levels of FGF21, BMD, but not other body composition parameters, attenuates the association between FGF21 level and age, suggesting the metabolic demand of the skeleton may provide a link between FGF21 and energy metabolism.

Context: Vitamin D status can influence insulin resistance. Objective: The aim of the study was to determine the prevalence of vitamin D deficiency in obese African-American (AA) adolescent females in a southeastern latitude and to determine the relationship of 25-hydroxyvitamin D [25(OH)D] with insulin and glucose dynamics. Design: We conducted a cross-sectional study in a University Children’s Hospital. Methods: Serum 25(OH)D, fasting glucose, PTH, serum calcium, serum lipids, serum transaminases, and C-reactive protein were assessed. Indices of insulin sensitivity and resistance were determined from an oral glucose tolerance test. Subjects were classified as vitamin D deficient or sufficient, based on the traditional vitamin D deficiency definition [serum 25(OH)D <20 ng/ml] and also by a lower 25(OH)D cut-point of 15 ng/ml or less. Results: A total of 51 AA adolescent females (body mass index, 43.3 ± 9.9 kg/m²; age, 14 ± 2 yr) were studied. Serum 25(OH)D concentrations were 20 ng/ml or less in 78.4% and 15 ng/ml or less in 60.8% of subjects. There were no significant group differences in the metabolic outcomes when subjects were classified using the traditional vitamin D deficiency definition. The Matsuda index of insulin sensitivity was significantly lower (P = 0.02), and insulin area under the curve was significantly higher (P = 0.04) in subjects with 25(OH)D concentrations of 15 ng/ml or less vs. those with higher concentrations. Conclusions: Vitamin D deficiency is highly prevalent in obese, AA female adolescents and may promote insulin resistance. Our data suggest that a 25(OH)D concentration of 15 ng/ml or less may be the threshold by which vitamin D deficiency confers negative effects on insulin sensitivity. The results suggest that 25(OH)D concentrations ≤15 ng/mL may be the threshold by which vitamin D deficiency confers negative effects on insulin sensitivity.