cholecalciferol and Hyperglycemia

Vitamin D may play an important role in modifying the risk of type 2 diabetes. Supplementation with cholecalciferol has been shown to improve β cell function and to attenuate the rise in glycated hemoglobin in people at high risk of diabetes. We examined whether circulating microRNAs (miRNAs) reflect disease progression and/or respond to vitamin D supplementation. We measured plasma levels of select miRNAs implicated in diabetes in people with prediabetes treated either with placebo (n=21) or 2000 U of cholecalciferol daily (n=21) for 4 months in the Calcium and Vitamin D for Diabetes Mellitus trial and compared the baseline-adjusted changes after correcting for age, body mass index, race, time of study entry (season) and baseline disposition index. Circulating levels of miR-7 (sixfold reduction, P=.01), miR-152 (1.5-fold increase, P=.03), and miR-192 (1.7-fold reduction, P=.026) displayed significant treatment-by-time interactions between the placebo- and the vitamin-D-treated groups. Plasma levels of miR-7 were reduced in the vitamin D and increased in the placebo group. The change in miR-152 positively correlated with the change in levels of the circulating metabolite 25-hydroxyvitamin D (r=0.33, P=.046) and negatively correlated with the change in glycated hemoglobin (r=-0.37, P=.024). The change in miR-192 positively correlated with the change in fasting glucose (r=0.41, P<.011). In conclusion, reduction of circulating miR-7 and miR-192, accompanied by elevation of miR-152, reflects a beneficial metabolic response to vitamin D treatment in people with prediabetes. These miRNAs may be useful biomarkers in diabetes prevention trials and other studies of vitamin D.

Topics: Aged; Biomarkers; Boston; Calcifediol; Cholecalciferol; Cohort Studies; Diabetes Mellitus, Type 2; Dietary Supplements; Disease Progression; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Longitudinal Studies; Male; MicroRNAs; Middle Aged; Prediabetic State; Risk

Our study aimed to examine the effects of daily consumption of vitamin D3-supplemented yogurt (VDY) drink on insulin resistance and lipid profiles in pregnant gestational diabetes mellitus (GDM) patients.. Participants aged 24-32 years in their second trimester were randomly assigned to consume either plain yogurt or VDY daily for 16 weeks. Metabolic and lipid profiles including levels of fasting plasma glucose (FPG), serum insulin, triacylglycerol (TAG), total cholesterol (TC) and low-density lipoprotein (LDL) were assessed at baseline (week 0) and end of trial (week 16).. After 16 weeks of intervention, insulin-related variables including FPG and serum insulin levels were markedly lower in VDY group participants. Insulin resistance parameters, such as homeostasis model of assessment of insulin resistance and β cell function, were also significantly reduced in VDY group participants. Moreover, levels of TAG, TC and LDL, as well as the TC to high-density lipoprotein ratio, had also significantly decreased in the VDY group.. Daily consumption of VDY drink improves insulin resistance and lipid profiles in women with GDM.

Topics: Adult; Beverages; Biomarkers; Calcifediol; China; Cholecalciferol; Diabetes, Gestational; Double-Blind Method; Female; Food, Fortified; Humans; Hyperglycemia; Hyperinsulinism; Hyperlipidemias; Insulin Resistance; Lipids; Maternal Nutritional Physiological Phenomena; Patient Dropouts; Pregnancy; Pregnancy Trimester, Second; Yogurt; Young Adult

The global prevalence of type 2 diabetes is increasing. Effective strategies to address this public health challenge are currently lacking. A number of epidemiological studies have reported associations between low concentrations of 25-hydroxy vitamin D and the incidence of diabetes, but a causal link has not been established. We investigate the effect of vitamin D supplementation on the metabolic status of individuals at increased risk of developing type 2 diabetes.. In a randomised double-blind placebo-controlled trial individuals identified as having a high risk of type 2 diabetes (non-diabetic hyperglycaemia or positive diabetes risk score) are randomised into one of three groups and given 4 doses of either placebo, or 100,000 IU Vitamin D₂ (ergocalciferol) or 100,000 IU Vitamin D₃ (cholecalciferol) at monthly intervals. The primary outcome measure is the change in glycated haemoglobin level between baseline and 4 months. Secondary outcome measures include blood pressure, lipid levels, apolipoproteins, highly sensitive C-reactive protein, parathyroid hormone (PTH) and safety of supplementation. and C-reactive protein. The trial is being conducted at two sites (London and Cambridge, U.K.) and a total of 342 participants are being recruited.. Trial data examining whether supplementation of vitamin D improves glycaemic status and other metabolic parameters in people at risk of developing type 2 diabetes are sparse. This trial will evaluate the causal role of vitamin D in hyperglycaemia and risk of type 2 diabetes. Specific features of this trial include recruitment of participants from different ethnic groups, investigation of the relative effectiveness and safety of vitamin D₂ and D₃ and an evidence based approach to determination of the dose of supplementation.. EudraCT2009-011264-11; ISRCTN86515510.

Topics: Adult; Aged; Blood Glucose; C-Reactive Protein; Cholecalciferol; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Ergocalciferols; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hyperglycemia; London; Male; Middle Aged; Risk; Treatment Outcome; Vitamins

Vitamin D deficiency is associated with an unfavorable metabolic profile in observational studies. The intention was to compare insulin sensitivity (the primary end point) and secretion and lipids in subjects with low and high serum 25(OH)D (25-hydroxyvitamin D) levels and to assess the effect of vitamin D supplementation on the same outcomes among the participants with low serum 25(OH)D levels.. Participants were recruited from a population-based study (the Tromsø Study) based on their serum 25(OH)D measurements. A 3-h hyperglycemic clamp was performed, and the participants with low serum 25(OH)D levels were thereafter randomized to receive capsules of 20,000 IU vitamin D(3) or identical-looking placebo twice weekly for 6 months. A final hyperglycemic clamp was then performed.. The 52 participants with high serum 25(OH)D levels (85.6 ± 13.5 nmol/L [mean ± SD]) had significantly higher insulin sensitivity index (ISI) and lower HbA(1c) and triglycerides (TGs) than the 108 participants with low serum 25(OH)D (40.3 ± 12.8 nmol/L), but the differences in ISI and TGs were not significant after adjustments. After supplementation, serum 25(OH)D was 142.7 ± 25.7 and 42.9 ± 17.3 nmol/L in 49 of 51 completing participants randomized to vitamin D and 45 of 53 randomized to placebo, respectively. At the end of the study, there were no statistically significant differences in the outcome variables between the two groups.. Vitamin D supplementation to apparently healthy subjects with insufficient serum 25(OH)D levels does not improve insulin sensitivity or secretion or serum lipid profile.

Topics: Adult; Aged; Calcifediol; Capsules; Carbohydrate Metabolism, Inborn Errors; Case-Control Studies; Cholecalciferol; Dietary Supplements; Female; Glucose Clamp Technique; Glycated Hemoglobin; Glycerol Kinase; Humans; Hyperglycemia; Hypoadrenocorticism, Familial; Insulin; Insulin Resistance; Insulin Secretion; Lipids; Male; Middle Aged; Triglycerides; Vitamin D Deficiency

Atypical antipsychotics are associated with an increased risk of hyperglycaemia, thus limiting their clinical use. This study focused on finding the molecular mechanism underlying antipsychotic-induced hyperglycaemia. First, we searched for drug combinations in the FDA Adverse Event Reporting System (FAERS) database wherein a coexisting drug reduced the hyperglycaemia risk of atypical antipsychotics, and found that a combination with vitamin D analogues significantly decreased the occurrence of quetiapine-induced adverse events relating diabetes mellitus in FAERS. Experimental validation using mice revealed that quetiapine acutely caused insulin resistance, which was mitigated by dietary supplementation with cholecalciferol. Further database analysis of the relevant signalling pathway and gene expression predicted quetiapine-induced downregulation of Pik3r1, a critical gene acting downstream of insulin receptor. Focusing on the phosphatidylinositol 3-kinase (PI3K) signalling pathway, we found that the reduced expression of Pik3r1 mRNA was reversed by cholecalciferol supplementation in skeletal muscle, and that insulin-stimulated glucose uptake into C2C12 myotube was inhibited in the presence of quetiapine, which was reversed by concomitant calcitriol in a PI3K-dependent manner. Taken together, these results suggest that vitamin D coadministration prevents antipsychotic-induced hyperglycaemia and insulin resistance by upregulation of PI3K function.

Topics: Animals; Antipsychotic Agents; Cell Line; Cholecalciferol; Class Ia Phosphatidylinositol 3-Kinase; Data Mining; Databases, Factual; Disease Models, Animal; Glucose Transporter Type 4; Humans; Hyperglycemia; Insulin Resistance; Mice; Quetiapine Fumarate; Signal Transduction; Vitamin D

Recent studies revealed a link between hypovitaminosis D3 and the risk for hyperglycemia. Further mechanistic and interventional investigations suggested a common reason for both conditions rather than a causal relationship. Exposure to sunlight is the most relevant source of vitamin D3 (25(OH)D), whereas adipose tissue is able to store relevant amounts of the lipophilic vitamin. Since running/bicycling leads to increased out-door time and alters physiological response mechanisms, it can be hypothesized that the correlation between hypovitaminosis D3 and hyperglycemia might be disturbed in outdoor athletes.. 47 elderly marathoners/bicyclists and 47 age/sex matched controls were studied in a longitudinal setting at baseline and after three years. HbA1c as a surrogate for (pre-)diabetic states was quantified via HPLC, 25(OH)D levels were measured by means of chemiluminescent assays. Physical performance was assessed by ergometry.. When adjusted for seasonal variations, 25(OH)D was significantly higher in athletes than in controls. 25(OH)D levels inversely correlated with triglycerides in both groups, whereas only in controls an association between high BMI or low physical performance with hypovitaminosis D3 had been found. Likewise, the presence of hypovitaminosis D3 at baseline successfully predicted hyperglycemia at the follow up examinations within the control group (AUC = 0.85, 95% CI [0.74, 0.96], p < .001, statistically independent from BMI), but not in athletes.. Our data suggest that mechanisms of HbA1c elevation might differ between athletes and controls. Thus, intense physical activity must be taken into account as a potential pre-analytic confounder when it is aimed to predict metabolic risk by vitamin D3 levels.

Topics: Aged; Athletes; Bicycling; Body Mass Index; Cholecalciferol; Ergometry; Exercise; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hyperglycemia; Longitudinal Studies; Male; Middle Aged; Prognosis; Prospective Studies; ROC Curve; Running; Seasons; Time Factors; Vitamin D Deficiency

Type 2 Diabetes is closely associated with our daily diets and has become a global health problem with an increasing number of patients. Recent observational and randomized studies on vitamin D3 suggested that higher plasma 25-hydroxyvitamin D3 [25(OH)D3] concentrations and more vitamin D3 intake are associated with lower risk of type 2 diabetes, which is characterized by postprandial hyperglycemia due to inappropriate glucose stimulated insulin secretion (GSIS) and its age-dependent increase of onset. However, rapid action of dietary vitamin D3 on the postprandial glucose profile has not been analyzed. When vitamin D3 is orally ingested in mice aged 12-14 weeks during an oral glucose tolerance test (OGTT), the serum glucose profile was not changed. In contrast, when OGTT was performed with old mice aged 30-34 weeks, the glucose profile was dramatically improved with increased insulin secretion, suggesting that orally ingested vitamin D3 potentiated GSIS in aged mice. Interestingly, there was also a significant increase in plasma GLP-1 in these aged mice. Our results suggest that orally ingested dietary vitamin D3 in aged mice improves glucose metabolism as a GLP-1 enhancer.

Topics: Administration, Oral; Aging; Animals; Blood Glucose; Cell Line; Cholecalciferol; Dietary Supplements; Enteroendocrine Cells; Glucagon-Like Peptide 1; Humans; Hyperglycemia; Insulin; Insulin Secretion; Male; Mice; Mice, Inbred BALB C; Treatment Outcome

Hyperglycemia without previous history of diabetes mellitus (DM) is observed in a high percentage of patients in intensive care units (ICU).. To determine the behavior of glycemia in nondiabetic patients with hyperglycemia by administering two micronutrients.. A clinical trial was conducted in 32 patients, 16 in the intervention group and 16 in the control group. To the intervention group was given, since the admission, the micronutrients vitamin D3 in doses of 1.000 international units (IU) and calcium in doses 1.000 mg every 24 hours, for a period of 72 hours.. No significant differences were observed in blood glucose income between the intervention and control groups (152,6 and 153,3 mg / dl, respectively p = 0,922), but after 72 hours the behavior of the glycemia decreased significantly in the intervention group compared to the control group (98,41 and 141,6 mg / dl respectively p 100 mg/ dl), showing that 2,29 patients should be treated to decrease an undesirable event (NNT).. The use of the analyzed micronutrients in critically ill patients with no previous diagnosis of diabetes requires more research that addresses te limitations posed here. Due to the limited literature found about similar studies, this investigation would provide another alternative for reducing hyperglycemia in these patients.. La hiperglucemia sin antecedentes previos de diabetes mellitus (DM) se observa en un alto porcentaje en pacientes de unidades de cuidado intensivo (UCI). Objetivo: Determinar el comportamiento de cifras de glucemia en pacientes no diabéticos con hiperglucemia mediante la administración de 2 micronutrientes. Metodología: se realizó un ensayo clínico a 32 pacientes, 16 en el grupo a intervenir y 16 en el grupo control. Al grupo intervenido se le administró desde su ingreso los micronutrientes vitamina D3 en dosis de 1.000 unidades internacionales (UI) y calcio en dosis de 1.000 mg cada 24 horas por un periodo de 72 horas. Resultados: no se observaron diferencias estadísticamente significativas en la glucemia de ingreso entre los grupos intervenidos y control (152,6 y 153,3 mg/dl respectivamente (p= 0,922), sin embargo a las 72 horas el comportamiento de las glucemias disminuyó significativamente en el grupo intervenido comparado con el grupo control (98,41 y 141,66 mg/dl respectivamente p= < 0,000). Así mismo, se evidenció que la intervención con vitamina D3 y Calcio redujo el riesgo (47%) de desarrollo del evento indeseado (glucemia > 100 mg/dl), mostrando que se deben tratar 2.29 pacientes para disminuir el evento indeseable (NNT). Conclusión: la utilización de los micronutrientes analizados en pacientes críticos sin diagnóstico previo de diabetes requiere de más investigaciones que contemplen las limitaciones aquí planteadas. Dada la poca literatura encontrada de estudios similares, esta investigación proporcionaría otra alternativa en la disminución de la hiperglucemia de éstos pacientes.

Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; Calcium, Dietary; Cholecalciferol; Critical Care; Female; Humans; Hyperglycemia; Intensive Care Units; Male; Middle Aged; Vitamins; Young Adult

It has previously been shown in this laboratory that vitamin D3 is essential for normal insulin secretion from the perfused rat pancreas. In this present study, the influence of vitamin D status on insulin secretion in vivo was investigated. Intravenous glucose tolerance tests were performed on conscious vitamin D-deficient rats (-D), vitamin D-replete rats fed ad libitum (+D AL), and vitamin D-replete rats pair fed to the D-deficient animals (+D PF). Vitamin D deficiency, easily recognizable by low daily dietary intake and depressed plasma calcium levels, was found to impair plasma glucose clearance as characterized by an elevated KG value (representing a function of the area beneath the tolerance curve). KG values for the +D AL, +D PF, and -D groups were 504 +/- 15, 480 +/- 46, and 641 +/- 28, respectively. The increase in KG corresponded to a significant reduction in glucose-mediated insulin secretion as compared to the +D animals. This difference appeared not to be related to the increase caloric intake associated with vitamin D repletion, since +D rats which had been pair fed to the -D animals also exhibited restored plasma insulin levels in response to glucose. Plasma phosphorus concentrations were comparable in all three groups, and thus this parameter is also unlikely to be a contributory factor in the observed phenomenon. Additional experiments were conducted to evaluate the involvement of hypocalcemia in the observed impaired glucose tolerance. Normalization of plasma calcium levels (from 4.8 mg/100 ml to 9.6/100 ml) of the -D rats, by dietary calcium and phosphorus manipulation, failed to improve glucose clearance (KG for -D normocalcemic rats = 639 +/- 61) or insulin secretion. These results support the concept that vitamin D plays a physiological role in insulin secretion, acting, at least in part, independently of nutritional factors and the prevailing plasma calcium and phosphorus concentrations.

Topics: Animals; Blood Glucose; Calcium; Cholecalciferol; Energy Intake; Glucose Tolerance Test; Hyperglycemia; Hyperparathyroidism, Secondary; Insulin; Insulin Secretion; Islets of Langerhans; Male; Phosphates; Rats; Vitamin D; Vitamin D Deficiency