Associations Between Serum 25-Hydroxyvitamin D, Insulin Sensitivity, Insulin Secretion, and β-Cell Function According to Glucose Tolerance Status

Serum 25-hydroxyvitamin D (25(OH)D) concentrations have been reported to increase following weight loss. Moreover, both weight loss and higher serum 25(OH)D concentrations have been associated with a lower risk of developing type 2 diabetes. The objective of the present study was to determine whether the increase in serum 25(OH)D concentration following weight loss is associated with improved insulin sensitivity, insulin secretion and disposition index (β-cell function). Data from two prospective lifestyle modification studies had been combined. Following a lifestyle-modifying weight loss intervention for 1 year, eighty-four men and women with prediabetes and a BMI ≥ 27 kg/m2 were divided based on weight loss at 1 year: < 5 % (non-responders, n 56) and ≥ 5 % (responders, n 28). The association between the change in serum 25(OH)D concentration and changes in insulin sensitivity (homeostasis model assessment of insulin sensitivity (HOMA%S) and Matsuda), insulin secretion (AUC of C-peptide) and disposition index after adjustment for weight loss was examined. Participants in the responders' group lost on average 9·5 % of their weight when compared with non-responders who lost only 0·8 % of weight. Weight loss in responders resulted in improved insulin sensitivity (HOMA%S, P= 0·0003) and disposition index (P= 0·02); however, insulin secretion remained unchanged. The rise in serum 25(OH)D concentration following weight loss in responders was significantly higher than that in non-responders (8·9 (sd 12·5) v. 3·6 (sd 10·7) nmol/l, P= 0·05). However, it had not been associated with amelioration of insulin sensitivity and β-cell function, even after adjustment for weight loss and several confounders. In conclusion, the increase in serum 25(OH)D concentration following weight loss does not contribute to the improvement in insulin sensitivity or β-cell function.

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Immediate enhancement of first-phase insulin secretion and unchanged glucose effectiveness in patients with type 2 diabetes after Roux-en-Y gastric bypass

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00506.2014 ◽

2015 ◽

Vol 308 (6) ◽

pp. E535-E544 ◽

Cited By ~ 37

Author(s):

Christoffer Martinussen ◽

Kirstine N. Bojsen-Møller ◽

Carsten Dirksen ◽

Siv H. Jacobsen ◽

Nils B. Jørgensen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Secretion ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Cell Function ◽

Β Cell ◽

Glucose Effectiveness ◽

Β Cell Function ◽

First Phase Insulin Secretion

Roux-en-Y gastric bypass surgery (RYGB) in patients with type 2 diabetes often leads to early disease remission, and it is unknown to what extent this involves improved pancreatic β-cell function per se and/or enhanced insulin- and non-insulin-mediated glucose disposal (glucose effectiveness). We studied 30 obese patients, including 10 with type 2 diabetes, 8 with impaired glucose tolerance, and 12 with normal glucose tolerance before, 1 wk, and 3 mo after RYGB, using an intravenous glucose tolerance test (IVGTT) to estimate first-phase insulin response, insulin sensitivity (Si), and glucose effectiveness with Bergman's minimal model. In the fasting state, insulin sensitivity was estimated by HOMA-S and β-cell function by HOMA-β. Moreover, mixed-meal tests and oral GTTs were performed. In patients with type 2 diabetes, glucose levels normalized after RYGB, first-phase insulin secretion in response to iv glucose increased twofold, and HOMA-β already improved 1 wk postoperatively, with further enhancements at 3 mo. Insulin sensitivity increased in the liver (HOMA-S) at 1 wk and at 3 mo in peripheral tissues (Si), whereas glucose effectiveness did not improve significantly. During oral testing, GLP-1 responses and insulin secretion increased regardless of glucose tolerance. Therefore, in addition to increased insulin sensitivity and exaggerated postprandial GLP-1 levels, diabetes remission after RYGB involves early improvement of pancreatic β-cell function per se, reflected in enhanced first-phase insulin secretion to iv glucose and increased HOMA-β. A major role for improved glucose effectiveness after RYGB was not supported by this study.

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Glucose metabolic disorder in Klinefelter syndrome: a retrospective analysis in a single Chinese hospital and literature review

BMC Endocrine Disorders ◽

10.1186/s12902-021-00893-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Shixuan Liu ◽

Tao Yuan ◽

Shuoning Song ◽

Shi Chen ◽

Linjie Wang ◽

...

Keyword(s):

Insulin Secretion ◽

Insulin Sensitivity ◽

Literature Review ◽

Glucose Tolerance ◽

Cell Function ◽

Klinefelter Syndrome ◽

Oral Glucose ◽

Model Assessment ◽

Β Cell ◽

Β Cell Function

Abstract Background We aimed to investigate the clinical characteristics and islet β-cell function in patients with Klinefelter syndrome (KS) and hyperglycemia. Methods This is a retrospective study. In total, 22 patients diagnosed with KS were identified from the electronic medical record system, including 9 patients with hyperglycemia (total patients with hyperglycemia, THG-KS group) and 5 hyperglycemic KS patients with oral glucose tolerance test (OGTT) results (HG-KS group). An additional 5 subjects with hyperglycemia and 5 normal glucose tolerance (NGT) subjects matched based on body mass index were included as the HG group and NGT group, respectively. Data from clinical and laboratory examinations were collected. We further performed a literature review of KS and hyperglycemia. Results We found that KS patients developed abnormal glucose metabolism earlier in life than those without KS, and the median age was 17 years, ranging from 10 years to 19 years. Six of 17 (35.3%) patients were diagnosed with diabetes mellitus and 3 of 17 (17.6%) patients were diagnosed with prediabetes. Among 10 patients with both fasting blood glucose and insulin results recorded, there were 8 out of 17 (47.1%) KS patients had insulin resistance. The prevalence of hypertension and dyslipidemia was higher in patients with hyperglycemia and KS than in patients with NGT KS. Compared with the HG group, insulin sensitivity levels were lower in HG-KS group, whereas homeostasis model assessment of β-cell function levels (p = 0.047) were significantly, indicating higher insulin secretion levels in the HG-KS group. Conclusions KS patients develop hyperglycemia earlier in life than those without KS and show lower insulin sensitivity and higher insulin secretion. These patients also have a higher prevalence of other metabolic diseases and may have different frequencies of developing KS-related symptoms.

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Vitamin D and Parathyroid Hormone Status in Pregnancy: Effect on Insulin Sensitivity, β-cell Function, and Gestational Diabetes Mellitus

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2014-2341 ◽

2014 ◽

Vol 99 (12) ◽

pp. 4506-4513 ◽

Cited By ~ 27

Author(s):

Caroline K. Kramer ◽

Balakumar Swaminathan ◽

Anthony J. Hanley ◽

Philip W. Connelly ◽

Mathew Sermer ◽

...

Keyword(s):

Vitamin D ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Vitamin D Deficiency ◽

Cell Function ◽

Β Cell ◽

Matsuda Index ◽

Β Cell Function ◽

Glucose Tolerance Status ◽

In Pregnancy

Context: Previous studies have yielded conflicting findings on the relationship between vitamin D deficiency/insufficiency and gestational diabetes mellitus (GDM). We hypothesized that PTH may be an underlying factor relevant to this potential association. Objective: This study sought to evaluate the effect of vitamin D and PTH status on insulin sensitivity, β-cell function, and glycemia in pregnancy. Setting and Design: Five-hundred-twenty-four women underwent a glucose challenge test (GCT) and oral glucose tolerance test (OGTT) in late second/early third trimester. The GCT/OGTT identified 142 women with GDM, 94 with gestational impaired glucose tolerance, 163 with an abnormal GCT and normal OGTT, and 125 with normal GCT and OGTT. Main Outcomes: Glycemia was assessed by glucose tolerance status and area under the glucose curve (AUCgluc) on the OGTT. Insulin sensitivity and β-cell function were assessed by Matsuda index and Insulin Secretion-Sensitivity Index-2 (ISSI-2), respectively. Results: There were 166 women (31.7%) with vitamin D deficiency (25-OH-D < 50 nmol/L), 178 (34%) with insufficiency (25-OH-D ≥ 50 nmol/L and < 75 nmol/L), and 180 (34.3%) with sufficiency (25-OH-D ≥ 75 nmol/L). Vitamin D status was not associated with Matsuda index, ISSI-2, AUCgluc, or glucose tolerance status. In contrast, ISSI-2 decreased and AUCgluc increased across ascending tertiles of PTH (P = .06 and P = .002, respectively). Indeed, the prevalence of GDM progressively increased from the first (22.6%) to second (25.8%) to third (33.5%) tertile of PTH (P < .001). On logistic regression analyses, the third tertile of PTH was independently associated with GDM (adjusted OR = 1.82; 95% CI, 1.09–3.02; P = .022), whereas vitamin D deficiency and insufficiency were not significant predictors of GDM. Conclusions: Increased PTH, rather than vitamin D deficiency/insufficiency, is independently associated with dysglycemia in pregnancy.

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Impaired β-cell function in the presence of reduced insulin sensitivity determines glucose tolerance status in acromegalic patients

Clinical Endocrinology ◽

10.1046/j.1365-2265.2000.00986.x ◽

2000 ◽

Vol 52 (5) ◽

pp. 549-555 ◽

Cited By ~ 83

Author(s):

Soji Kasayama ◽

Michio Otsuki ◽

Miki Takagi ◽

Hiroshi Saito ◽

Satoru Sumitani ◽

...

Keyword(s):

Insulin Sensitivity ◽

Glucose Tolerance ◽

Cell Function ◽

Β Cell ◽

Β Cell Function ◽

Glucose Tolerance Status

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The Disposition Index Does Not Reflect β-Cell Function in IGT Subjects Treated With Pioglitazone

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2014-1515 ◽

2014 ◽

Vol 99 (10) ◽

pp. 3774-3781 ◽

Cited By ~ 22

Author(s):

Ralph A. DeFronzo ◽

Devjit Tripathy ◽

Muhammad Abdul-Ghani ◽

Nicolas Musi ◽

Amalia Gastaldelli

Keyword(s):

Insulin Secretion ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Plasma Insulin ◽

Cell Function ◽

Insulin Response ◽

Curvilinear Relationship ◽

Β Cell ◽

Β Cell Function ◽

Plasma Insulin Response

Abstract Aims and Hypothesis: The insulin secretion/insulin resistance (IR) (disposition) index (ΔI/ΔG ÷ IR, where Δ is change from baseline, I is insulin, and G is glucose) is commonly used as a measure of β-cell function. This relationship is curvilinear and becomes linear when log transformed. ΔI is determined by 2 variables: insulin secretion rate (ISR) and metabolic clearance of insulin. We postulated that the characteristic curvilinear relationship would be lost if Δ plasma C-peptide (ΔCP) (instead of Δ plasma insulin) was plotted against insulin sensitivity. Methods: A total of 441 individuals with impaired glucose tolerance (IGT) from ACT NOW received an oral glucose tolerance test and were randomized to pioglitazone or placebo for 2.4 years. Results: Pioglitazone reduced IGT conversion to diabetes by 72% (P < .0001). ΔI/ΔG vs the Matsuda index of insulin sensitivity showed the characteristic curvilinear relationship. However, when ΔCP/ΔG or ΔISR/ΔG was plotted against the Matsuda index, the curvilinear relationship was completely lost. This discordance was explained by 2 distinct physiologic effects that altered plasma insulin response in opposite directions: 1) increased ISR and 2) augmented metabolic clearance of insulin. The net result was a decline in the plasma insulin response to hyperglycemia during the oral glucose tolerance test. These findings demonstrate a physiologic control mechanism wherein the increase in ISR ensures adequate insulin delivery into the portal circulation to suppress hepatic glucose production while delivering a reduced but sufficient amount of insulin to peripheral tissues to maintain the pioglitazone-mediated improvement in insulin sensitivity without excessive hyperinsulinemia. Conclusions: These results demonstrate the validity of the disposition index when relating the plasma insulin response to insulin sensitivity but underscore the pitfall of this index when drawing conclusions about β-cell function, because insulin secretion declined despite an increase in the plasma insulin response.

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Identification of insulin secretory defects and insulin resistance during oral glucose tolerance test in a cohort of cystic fibrosis patients

Acta Endocrinologica ◽

10.1530/eje-10-1003 ◽

2011 ◽

Vol 165 (1) ◽

pp. 69-76 ◽

Cited By ~ 21

Author(s):

A Battezzati ◽

A Mari ◽

L Zazzeron ◽

G Alicandro ◽

L Claut ◽

...

Keyword(s):

Insulin Secretion ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Glucose Tolerance Test ◽

Cell Function ◽

Tolerance Test ◽

Oral Glucose ◽

Oral Glucose Tolerance ◽

Β Cell ◽

Β Cell Function

BackgroundCystic fibrosis (CF)-related diabetes is a leading complication of CF and is associated with pulmonary and nutritional deterioration, years before an evident hyperglycemia, possibly because of insulin deficiency and resistance.AimTo evaluate glucose tolerance, insulin secretion, and insulin sensitivity by a widely applicable method suitable for accurate and prospective measurements in a CF population.MethodsA total of 165 CF subjects (80 females) aged 17±5 years and 18 age- and sex-matched healthy controls (CON) received an oral glucose tolerance test with glucose, insulin and C-peptide determinations. Insulin sensitivity was defined on the basis of glucose and insulin concentrations using the oral glucose insulin sensitivity index, whereas β-cell function was determined on the basis of a model relating insulin secretion (C-peptide profile) to glucose concentration.ResultsFifteen percent of CF patients had glucose intolerance and 6% had diabetes without fasting hyperglycemia and 3% had diabetes with fasting hyperglycemia. β-cell function was reduced in CF patients compared with CON (70.0±4.1 vs 117.9±11.6 pmol/min per m2 per mM, P<0.001) and decreased significantly with age by −2.7 pmol/min per m2 per mM per year (confidence interval (CI) −4.5 to −0.82), i.e. almost 4% yearly. The early insulin secretion index was also reduced. Insulin sensitivity was similar to CON. CF patients who attained glucose tolerance comparable to CON had lower β-cell function and higher insulin sensitivity.ConclusionThe major alteration in insulin secretion and insulin sensitivity of CF patients is slowly declining β-cell function, consisting of delayed and reduced responsiveness to hyperglycemia, that in CF patients with normal glucose tolerance may be compensated by an increased insulin sensitivity.

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