Elevated Fasting Insulin Levels Research Articles

Environmental tobacco use and indicators of metabolic syndrome in Chinese adults.

Exposure to environmental tobacco smoke (ETS) is a widespread source of nicotine exposure, and an estimated 540 million Chinese are exposed to ETS in mainland China. We aimed to investigate associations of ETS exposure and metabolic syndrome (MetS) as well as its individual components independent of active smoking status in Chinese adults. A cross-sectional data of 304 randomly selected Chinese households with fourth (elementary school) and seventh (middle school) graders in Qingdao city was used. Assessments of fat mass, metabolic biomarkers, personal history of illness, and health behaviors were conducted. Proportions of current smokers were 3% in women and 60.5% in men, and more men reported exposure to ETS 5-7 days per week than women (60.8% vs. 48.1%). Exposure to ETS was significantly associated with enhanced risks of MetS (odds ratio [OR] = 2.8, p = .01), hypertriglyceridemia (OR = 2.1, p = .02), and central obesity (OR = 2.7, p < .001) and reduced levels of high-density lipoprotein cholesterol (OR = 1.9, p = .02) and elevated mean levels of fasting insulin (p < .01). These observed associations were independent of active smoking status and were successfully replicated in female never-smokers. Results of our study support the hypothesis that ETS exposure is independently associated with MetS and its individual components. Further large-scale studies with longitudinal design and objective assessment of ETS exposure are needed to elucidate the underlying mechanisms and the causal effects of passive smoking on MetS. Findings of this work emphasize the importance of developing community intervention to reduce smoking, ETS, and promote healthy lifestyle.

Characteristics of Adolescents Presenting to a Multidisciplinary Clinic for Polycystic Ovarian Syndrome

Objective To characterize patients referred to the adolescent polycystic ovarian syndrome (PCOS) clinic at the American Family Children's Hospital, University of Wisconsin, Madison, Wisconsin. Design Chart review of patients seen in the first 33 months for details of initial presentation, age, body mass index (BMI), menstrual pattern, clinical and laboratory features of androgen excess, insulin resistance, and dyslipidemia. Setting Multidisciplinary clinic for adolescents with PCOS at the American Family Children's Hospital, Madison, Wisconsin. Participants Adolescent girls with PCOS. Results Seventy patients (84% Caucasian) presented with an average age at referral of 16.2 years (range 11-22 y). Eighty four percent had a BMI > the 85 th percentile and 70% had a BMI > 95 th percentile. Menstrual pattern was quite varied, with some patients having primary amenorrhea, and over 50% experiencing hirsutism. There were 3 cases of type 2 diabetes, and over half of the patients had elevated fasting insulin levels and low HDL levels. Conclusion Polycystic ovarian syndrome is a complex and heterogeneous disorder that requires multidisciplinary expertise. Knowing the unique features of the adolescent with PCOS and metabolic risks should permit earlier intervention with intensive counseling and medical therapy to address current health concerns and prevent future co-morbidities.

Metabolic Abnormalities and Cardiovascular Risk Factors in Children with Myositis

To characterize the metabolic abnormalities and risk factors for future cardiovascular disease in children with myositis. Seventeen patients with severe juvenile myositis, primarily referred because of refractory disease, were examined with standardized disease activity and damage measures. Body mass index, fasting insulin and lipid levels, 2-hour oral glucose tolerance test results, and cytokine levels were obtained. Most patients (71%) had blood pressures >75th percentile; 23.5% of patients had hypertension; and body mass index was >85th percentile in 47%. Metabolic abnormalities were also frequent: 41.2% had an elevated fasting insulin level, 47.1% had hypertriglyceridemia, and 25% met criteria for the metabolic syndrome. Although insulin resistance was common (on the basis of homeostasis model assessment and glucose-to-insulin ratio), insulin secretion appeared to be unaffected. Thigh muscle damage assessed with magnetic resonance imaging significantly correlated with fasting insulin level, glucose level, and glucose-to-insulin ratio. Glucose indices also correlated with the proinflammatory cytokines interleukin (IL)-2 and IL-12 and inversely with anti-inflammatory cytokines IL-1RA and IL-10. In this referral cohort of children with severe juvenile myositis, metabolic abnormalities and predictors of cardiovascular disease were common, suggesting an increased risk of future cardiovascular disease. Indicators of insulin resistance correlated with muscle damage on magnetic resonance imaging and proinflammatory cytokines and inversely with anti-inflammatory cytokines.

Basal-State Hyperinsulinemia in Healthy Normoglycemic Adults Is Predictive of Type 2 Diabetes Over a 24-Year Follow-Up

OBJECTIVEWe examined the predictive value of hyperinsulinemia in the basal state on the 24-year progression from normoglycemia to dysglycemia.RESEARCH DESIGN AND METHODSA sample of 515 normoglycemic men and women were studied again after 24 years for glycemic status.RESULTSHalf of the participants developed dysglycemia: 11.1% progressed to impaired fasting glucose (IFG), 9.9% to impaired glucose tolerance (IGT), 4.5% to both IFG and IGT, and another 24.3% to type 2 diabetes. Elevated levels of overnight fasting (basal) insulin, triglycerides, BMI ≥27 kg/m2, fasting blood glucose, blood pressure, North African or Yemenite background, and male sex each favored conversion to dysglycemia after 24 years. In multiple ordered logistic regression analysis, the most significant predictor of progression to dysglycemia was hyperinsulinemia (upper quintile), after adjusting for BMI, ethnic origin, sex, age, smoking, physical activity, blood pressure, and triglycerides.CONCLUSIONSBasal hyperinsulinemia in normoglycemic adults constitutes an independent risk factor for developing dysglycemia over 24 years.

Genetic factors for resistance to diet-induced obesity and associated metabolic traits on mouse chromosome 17.

Obesity is associated with increased susceptibility to dyslipidemia, insulin resistance, and hypertension, a combination of traits that comprise the traditional definition of the metabolic syndrome. Recent evidence suggests that obesity is also associated with the development of nonalcoholic fatty liver disease (NAFLD). Despite the high prevalence of obesity and its related conditions, their etiologies and pathophysiology remains unknown. Both genetic and environmental factors contribute to the development of obesity and NAFLD. Previous genetic analysis of high-fat, diet-induced obesity in C57BL/6J (B6) and A/J male mice using a panel of B6-Chr(A/J)/NaJ chromosome substitution strains (CSSs) demonstrated that 17 CSSs conferred resistance to high-fat, diet-induced obesity. One of these CSS strains, CSS-17, which is homosomic for A/J-derived chromosome 17, was analyzed further and found to be resistant to diet-induced steatosis. In the current study we generated seven congenic strains derived from CCS-17, fed them either a high-fat, simple-carbohydrate (HFSC) or low-fat, simple-carbohydrate (LFSC) diet for 16 weeks and then analyzed body weight and related traits. From this study we identified several quantitative trait loci (QTLs). On a HFSC diet, Obrq13 protects against diet-induced obesity, steatosis, and elevated fasting insulin and glucose levels. On the LFSC diet, Obrq13 confers lower hepatic triglycerides, suggesting that this QTL regulates liver triglycerides regardless of diet. Obrq15 protects against diet-induced obesity and steatosis on the HFSC diet, and Obrq14 confers increased final body weight and results in steatosis and insulin resistance on the HFSC diet. In addition, on the LFSC diet, Obrq 16 confers decreased hepatic triglycerides and Obrq17 confers lower plasma triglycerides on the LFSC diet. These congenic strains provide mouse models to identify genes and metabolic pathways that are involved in the development of NAFLD and aspects of diet-induced metabolic syndrome.

Determination of Reference Values for Elevated Fasting and Random Insulin Levels and their Associations with Metabolic Risk Factors Among Rural Pakistanis from Sindh Province

To assess insulin levels and their association with metabolic risk factors (family history of diabetes, abnormal glucose tolerance, hypertension, overweight and android obesity) among a representative group of Pakistan. The study data was taken from the database of a population-based survey conducted in Sindh Province, Pakistan, in 1994 to assess the prevalence of diabetes mellitus and impaired glucose tolerance (IGT). Through stratified random sampling; oral glucose tolerance tests were performed in 967 adults; every fifth sample was estimated for fasting and random (2-hour post-75 gm glucose load) insulin levels. The total number of metabolic risk factors was counted for each subject, and their association with insulin levels studied. Of the 130 subjects, 56.1% were females and 95.4% were Sindhi. The mean age of males and females was 43.84 and 40.61 years, respectively. Family history for diabetes and frequency of overweight had significant positive associations with both fasting and random insulin levels (P < 0.05). Association between hypertension and insulin levels was significant only for random insulin levels, and between android obesity, abnormal glucose tolerance, or male gender and insulin levels only for fasting insulin levels (P < 0.05). Metabolic risk factors had significant positive associations with both fasting (r = 0.351 P = 0.000) as well as random insulin levels (r = 0.364 P = 0.000). This paper provides baseline pioneering information applicable to the Pakistani population. Furthermore, the observations made in this study about differences in association of fasting or random insulin levels with various metabolic risk factors highlight the possibility of using either of them for risk assessment. This finding needs to be assessed in a larger and nationally representative sample.

Elevated Fasting Insulin And Crp Levels Are Linked With Obesity And Low Aerobic Fitness In Young Qatari Boys.

There is a concern around the world, including the Arabic countries, of young people's lifestyle and its effect on health later in life. Early markers for a possible elevated risk to develop metabolically related chronic diseases are sought for but it is still unknown which of them is the most sensitive. Moreover, the primary life style factor focused on, has been nutrition and overweight with only little attention being paid to physical inactivity and low maximal oxygen uptake. PURPOSE: To screen for a large number of "metabolic" markers in the blood in young Qatari boys with concomitant measures of body composition and maximal oxygen uptake. METHODS: Forty, 10-13 years old boys were studied. A fasting blood sample was taken and in addition to their height and weight a DEXA scan was used to assess body composition. A step test was performed to exhaustion to measure aerobic fitness. RESULTS: The BMI ranged from 14 to 36 kg/m2 with a mean of 22 kg/m2 (median 20) and the aerobic fitness ranged from 14 to 36ml/kg/min with mean value of 30 ml/kg/min (median 32). Equally strong and significant correlations were found for both BMI and aerobic fitness and fasting insulin level with a four fold difference comparing the 20% "worst" and the 20% "best" (4 vs16 microU/ml. The 20% in the middle were in between (8 microU/ml). Also the CRP levels were significantly correlated with BMI and aerobic fitness, with a slightly stronger link to BMI. However the difference in absolute values between those with the highest and lowest BMI and aerobic fitness was 4 fold (2 vs 8 mg/l) and with the middle group being similar to the fit and non-obese boys. The pattern and strength for the correlations were the same for fat % and BMI. No relationships were found for measures of body composition and aerobic fitness to any of the other markers studied (chol, LDL- and HDL-chol, TG, glucose, HbA1c, homocysteine). CONCLUSIONS: Fasting insulin and to some extent CRP may be sensitive early markers of an emerging metabolic deterioration but in this group of boys it is impossible to dissociate between overweight and a low aerobic fitness playing the largest role. Longitudinal studies are needed to track the long term effect of these factors upon metabolic deterioration.

Ghrelin Regulates Insulin Release and Glycemia: Physiological Role and Therapeutic Potential

Insulin release from pancreatic islet beta-cells is stimulated by glucose. Glucose-induced insulin release is potentiated or suppressed by hormones and neural substances. Ghrelin, a novel acylated 28-amino acid peptide isolated from stomach, is the endogenous ligand for the growth hormone (GH) secretagogue-receptor (GHS-R). Circulating ghrelin is produced predominantly in stomach. Ghrelin is a potent stimulator of GH release and feeding as well as exhibiting positive cardiovascular effects. In relation to the glucose metabolism, initial studies indicated that low plasma ghrelin levels are associated with elevated fasting insulin levels, insulin resistance, and obesity. It has recently been demonstrated that ghrelin suppresses glucose-induced insulin release via G alpha(i2) subtype of GTP-binding proteins and delayed outward K(+) (Kv) channels, representing a novel signaling mechanism, and that the ghrelin originating from islets regulates insulin release and thereby glycemia. Furthermore, elimination of ghrelin enhances insulin release to prevent or ameliorate glucose intolerance in high-fat diet fed mice and ob/ob mice. This review focuses on the physiological roles of ghrelin in regulating insulin release and glycemia, the insulinostatic mechanisms of ghrelin in islet beta-cells, and the potential of ghrelin-GHS-R system as the therapeutic target to treat type 2 diabetes.

Endurance training alleviates PRKCQ genotype-related metabolic abnormalities

Protein kinase C theta (PRKCQ) knock-out mice manifest decreased energy expenditure as compared to wild-type mice due to reduced spontaneous physical activity and they develop obesity and insulin resistance on a high-fat diet. PURPOSE: We tested the hypothesis that DNA sequence variation in the human PRKCQ gene locus is associated with adiposity and plasma insulin phenotypes in the sedentary state and in response to endurance training in the HERITAGE Family Study. METHODS: Fasting plasma insulin, MINMOD-derived insulin sensitivity (SI), body composition (underwater weighing), and abdominal visceral fat (AVF; CT scan) were measured in the sedentary state (baseline) and after a 20-week endurance training program in 247 Blacks and 476 Whites. Nine PRKCQ tagSNPs were genotyped using the FP-TDI method. RESULTS: In Blacks, both baseline fasting insulin (p<0.022; adjusted for age, sex, and BMI) and AVF (p<0.001; adjusted for age, sex, and fat mass) were associated with two SNPsatthe5'endofthegene(rs541709, rs571715), whereas a SNP in intron 3 (rs510745) was associated with baseline SI (p=0.005). For insulin and SI, the associations were observed in offspring (p<0.0006) but not in parents (genotype-by-generation interactions p<0.05). The same 5′ SNPs were associated with AVF and fasting insulin training responses in Black offspring (p<0.004): the common allele homozygotes having the highest AVF and fasting insulin levels at baseline but showing the greatest training-induced reductions in both traits. In White offspring, both rs541709 (p=0.045) and rs510745 (p=0.025), as well as rs677986 in intron 15 (p=0.007) were associated with fasting insulin at baseline. Baseline AVF was not associated with the PRKCQ SNPs in Whites. However, the Leu330Pro variant (rs2236379) in exon 8 showed significant association with training-induced changes in AVF (p=0.022). The PRKCQ SNPs were not associated with body composition traits in either ethnicity. CONCLUSION: Our data suggest that DNA sequence variation at the human PRKCQ locus increases the risk of accumulating intra-abdominal fat and having elevated fasting insulin levels in sedentary young adults. However, regular physical activity seems to counteract to some extent both PRKCQ locus -related metabolic disturbances.

Comparative effectiveness of carvedilol and propranolol on glycemic control and insulin resistance associated withl-thyroxin-induced hyperthyroidism — an experimental study

The present study was undertaken to investigate the effectiveness of adrenergic antagonists carvedilol and propranolol on L-thyroxin-induced cardiovascular and metabolic disturbances in rats. Treatment with L-thyroxin sodium (75 mg/kg body mass, s.c., every alternate day for 3 weeks), produced a significant increase in food and water intake, body temperature, heart rate, systolic blood pressure, along with an increase in serum T3, T4, and triglyceride levels. Besides a significant reduction in body mass, serum levels of TSH and cholesterol were also reduced following L-thyroxin treatment. Carvedilol (10 mg/kg body mass, orally) and propranolol (10 mg/kg body mass, i.p.) administered daily in the third week to 2 separate groups of L-thyroxin-treated animals reversed thyroxin-induced loss in body mass and rise in body temperature, blood pressure, and heart rate. Propranolol treatment increased TSH levels and decreased T3 and T4 levels in hyperthyroid animals, whereas carvedilol did not produce any effect on thyroid hormones. Carvedilol treatment reversed thyroxin induced hypertriglyceridemia, whereas propranolol treatment had no effect. Both carvedilol and propranolol prevented decrease in cholesterol levels induced by thyroxine. Compared with normal animals, L-thyroxin-treated animals showed a state of hyperglycemia, hyperinsulinaemia, impaired glucose tolerance, and insulin resistance, as inferred from elevated fasting serum glucose and insulin levels, higher area under the curve over 120 min for glucose, and decreased insulin sensitivity index (KITT). Propranolol and carvedilol treatment significantly decreased fasting serum glucose levels. Treatment with propranolol did not alter serum insulin levels, area-under-the-curve glucose, or KITT values. However, treatment with carvedilol significantly reduced area-under-the-curve glucose, decreased fasting serum insulin levels and significantly increased KITT values. In conclusion, carvedilol appears to produce favorable effects on insulin sensitivity and glycemic control and can therefore be considered as more efficacious adjunctive treatment than propranolol in hyperthyroidism.

Direct metabolic effects of risperidone and olanzapine in Japanese schizophrenic patients

Direct metabolic effects of risperidone and olanzapine in Japanese schizophrenic patients

Dietary Energy Density Is Associated With Obesity and the Metabolic Syndrome in U.S. Adults

Rising obesity rates have been linked to the consumption of energy-dense diets. We examined whether dietary energy density was associated with obesity and related disorders including insulin resistance and the metabolic syndrome. We conducted a cross-sectional study using nationally representative data of U.S. adults > or =20 years of age from the 1999-2002 National Health and Nutrition Examination Survey (n = 9,688). Dietary energy density was calculated based on foods only. We used a series of multivariate linear regression models to determine the independent association between dietary energy density, obesity measures (BMI [in kilograms per meters squared] and waist circumference [in centimeters]), glycemia, or insulinemia. We used multivariate Poisson regression models to determine the independent association between dietary energy density and the metabolic syndrome as defined by the National Cholesterol and Education Program (Adult Treatment Panel III). Dietary energy density was independently and significantly associated with higher BMI in women (beta = 0.44 [95% CI 0.14-0.73]) and trended toward a significant association in men (beta = 0.37 [-0.007 to 0.74], P = 0.054). Dietary energy density was associated with higher waist circumference in women (beta = 1.11 [0.42-1.80]) and men (beta = 1.33 [0.46-2.19]). Dietary energy density was also independently associated with elevated fasting insulin (beta = 0.65 [0.18-1.12]) and the metabolic syndrome (prevalence ratio = 1.10 [95% CI 1.03-1.17]). Dietary energy density is an independent predictor of obesity, elevated fasting insulin levels, and the metabolic syndrome in U.S. adults. Intervention studies to reduce dietary energy density are warranted.

Amelioration of insulinoma symptoms in pregnancy

Background: Insulinomas are rare, mostly benign neuroendocrine tumours with an incidence of approximately four cases per million person-years. Only isolated case reports of insulinomas occurring in pregnancy have been documented. Case Report: A 34-year-old woman (gravida 1, para 1) presented with severe hypoglycaemia after delivery. Endocrine testing was consistent with insulinoma showing elevated fasting insulin, pro-insulin, and C-peptide levels in the setting of hypoglycaemia. The patient was managed with glucose monitoring, frequent carbohydrate-rich meals, and continuous intravenous glucose infusions. Endoscopic ultrasonography, magnetic resonance imaging, and selective arterial calcium stimulation confirmed a mass in the corpus of the pancreas. During surgical exploration using intraoperative ultrasonography the pancreatic mass was removed. Histology was consistent with a benign insulinoma according to the World Health Organization (WHO) classification. Postoperatively, all hypoglycaemic symptoms resolved with no further treatment. Conclusion: Insulinoma may be masked by pregnancy due to insulin-antagonist hormones inducing insulin resistance. Insulinoma in pregnancy, though very rare, should be included in the differential diagnosis of postpartum hypoglycaemia.

Sex differences in the relation of depressive symptoms, hostility, and anger expression to indices of glucose metabolism in nondiabetic adults.

This study examined the relation of depressive symptomatology, hostility, and anger expression to indices of glucose metabolism and tested whether gender moderates these associations in a sample of 135 healthy, nondiabetic adults (75 men, 60 women). The severity of depressive symptoms, hostility, and anger expression was positively associated with estimated insulin resistance (IR) and insulin in women but not in men. Anger expression was positively associated with glucose in women only. A summary score of depressive symptoms, hostility, and anger expression was positively associated with estimated IR, insulin, and glucose in women but not in men. Hence, in women, IR and elevated levels of fasting insulin and glucose may be one pathophysiological mechanism mediating the increased risk of cardiovascular disease and Type 2 diabetes associated with these psychological attributes.

Use of Metformin for Ovulation Induction in Women Who Have Polycystic Ovary Syndrome With or Without Evidence of Insulin Resistance

ObjectiveTo determine whether women with polycystic ovary syndrome (PCOS) and abnormal insulin levels treated with metformin had different rates of ovulation and pregnancy from women with PCOS and normal insulin levels. MethodsThe outcomes of treatment with metformin in 146 infertile women with PCOS were analyzed using a retrospective cohort study design. Baseline characteristics and initial blood work results were recorded. The follow-up period was three months, and the primary outcome was ovulation. ResultsOf the 146 women with PCOS, one third had elevated fasting insulin levels. After treatment with metformin, cumulative rates of ovulation were similar in women with elevated fasting serum insulin levels (48.8%) and those with normal levels (44.7%). Rates of ovulation were also similar in women with normal and abnormal glucose to insulin ratios. There was no difference in cumulative pregnancy rates based on fasting insulin levels. A fasting insulin level above 20mU/L correlated with an abnormal glucose to insulin ratio (98%). ConclusionIn anovulatory women with PCOS, fasting insulin levels and glucose to insulin ratios do not predict the ovulatory response to metformin.

Vascular Structure and Function in Women: Relationship with Body Mass Index

The purpose of the present study was to compare endothelial function in lean (body mass index [BMI]=18.0-24.9 kg/m2); overweight (BMI=25-29.9 kg/m2); and obese (BMI>30 kg/m2), healthy, eumenorrheic women. Eighteen lean, 22 overweight, and 19 obese eumenorrheic middle-aged women were studied. Vascular structure and function were assessed via non-invasive ultrasound imaging of the carotid and brachial arteries. Body composition, blood pressure, fasting blood lipids, glucose, and insulin also were measured. The groups demonstrated significantly (p<0.001) different mean values for total body, lean body, and fat masses. The obese group demonstrated significantly (p<0.05) elevated fasting glucose and insulin levels and lower high-density lipoprotein levels as compared to the lean group. The overweight group also demonstrated elevated fasting glucose levels as compared to the lean group (p<0.05) with no significant difference from the obese group. Only systolic blood pressure differed among the three groups, being elevated in the obese group compared to the lean group (p<0.05). The obese group demonstrated significantly (p<0.05) elevated carotid artery lumen diameter, carotid artery wall cross-sectional area, and brachial artery lumen diameter with significantly (p<0.05) lower flow-mediated dilation as compared to the lean group. The overweight group demonstrated elevated carotid artery wall cross-sectional area and brachial artery lumen diameter as well as lower flow-mediated dilation as compared to the lean group (p<0.05). The results of this study support the hypothesis that carotid artery wall cross-sectional area is elevated and flow-mediated dilation reduced in overweight and obese eumennorheic women as compared to lean counterparts in relation to BMI classification.

Effect of fasting insulin level on circulating Th1 and Th2 cytokines in patients with systemic lupus erythematosus

Objective It has been increasingly recognized patients with systemic lupus erythematosus (SLE) have various cytokine abnormalities. However, both Th1- and Th2-derived cytokines can participate in promoting or inhibiting autoimmune disease depending on characteristic of disease. We previously reported that SLE patients have a higher risk of insulin resistance and abnormal insulin secretion. The objective of this study was to examine effects of fasting insulin level on circulating Th1- and Th2-derived cytokines in SLE patients. Method Plasma levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-4, IL-6, IL-10, IL-12, and IL-18 were determined by enzyme-linked immunosorbent assay using commercial kits in a total of 70 female SLE patients. All patients were further classified into two subgroups (SLE with hyperinsulinemia, n = 21 vs. SLE controls, n = 49) based on fasting insulin level. Results There were no statistical differences in plasma levels of Th2 cytokines between two SLE subgroups, but SLE patients with hyperinsulinemia compared with SLE controls had significantly higher plasma levels of TNF-α and IL-18 according to Mann-Whitney U test. In addition, fasting insulin level correlated positively and significantly with TNF-α and IL-18 in all SLE patients based on Spearman’s correlation analysis. Conclusion Elevated fasting insulin levels played a predominant role in mediating proinflammatory cytokines including TNF-α and IL-18 in patients with SLE.

9: Elevated fasting insulin levels observed in obese teens using medroxyprogesterone

9: Elevated fasting insulin levels observed in obese teens using medroxyprogesterone

β-Cell Function, Insulin Sensitivity, and Glucose Tolerance in Obese Diabetic and Nondiabetic Adolescents and Young Adults

Type 2 diabetes mellitus (T2DM) is estimated to account for 10-45% of incident pediatric diabetes cases. Our objective was to characterize the metabolic defects underlying T2DM in adolescents and young adults. We conducted a cross-sectional study of islet function and insulin sensitivity in 16 adolescents with T2DM and 13 obese (OB) and 13 lean (LN) age-matched nondiabetic subjects at a University Medical Center. We provided oral and iv glucose tolerance tests. We measured insulin and glucagon levels, insulin sensitivity, acute insulin responses to iv glucose, and the ratio of proinsulin to immunoreactive insulin. The diabetic subjects had elevated fasting insulin levels and significantly reduced insulin sensitivity (P < 0.05). The acute insulin response to iv glucose was comparable in the T2DM and LN groups (P < 0.05 for the OB vs. LN and T2DM), but insulin secretion adjusted for insulin resistance, the disposition index, was severely impaired in the diabetic subjects (P < 0.05 for the T2DM vs. LN and OB). The ratio of proinsulin to immunoreactive insulin did not differ among the three groups in the basal or stimulated state. Plasma glucagon levels were comparable before and after ingestion of glucose. These findings demonstrate that diabetic adolescents have significant insulin resistance, even compared with subjects of similar obesity and body fatness, and impaired insulin secretion relative to their degree of insulin resistance. However, the adolescent diabetic subjects retained a first-phase insulin response to glucose that was comparable to lean controls and did not have hyperproinsulinemia or hyperglucagonemia.

Prediction of gestational diabetes mellitus in a high‐risk group by insulin measurement in early pregnancy

We hypothesized that an increased serum insulin level in early pregancy reflects an increased demand on the compensatory capacity of the pregnant woman, and can serve as a predictor of gestational diabetes mellitus (GDM). A 2-h, 75-g oral glucose tolerance test (OGTT), with fasting and 2-h postprandial serum insulin determination, was performed in 71 pregnant women with one or more risk factors for GDM before gestation week 16. In 64 patients, subsequent OGTTs were performed at gestation weeks 24-28, and in the event of a negative result, at gestation weeks 32-34. Insulin determination at fasting and at 120 min had sensitivities of 69.2% and 92.3%, and specificities of 96.4% and 85.7%, respectively, for the prediction of GDM at gestation weeks 24-28. The sensitivities decreased to 33.3% and 75.0%, respectively, for the prediction of GDM at gestation weeks 32-34. Insulin determination at fasting and at 120 min had positive predictive values of 0.90 and 0.75, respectively, for the prediction of GDM at gestation weeks 32-34. The negative predictive values of fasting and 120-min serum insulin determination at gestation week < or = 16 were 0.87 and 0.96, respectively, for the prediction of GDM at gestation weeks 24-28. Increased serum insulin levels both at fasting and 120 min before gestation week 16 were very strong predictive factors for GDM by gestation weeks 32-34 with an odds ratio of 16.6 and 13.3, respectively. Serum insulin determination at gestation week < or = 16 is an easy and reliable method with which to predict GDM in a high-risk group. Despite a negative OGTT, patients with an elevated fasting and/or 120-min serum insulin level at gestation week < or = 16 should be managed in the same way as those with GDM. Considering the very high negative predictive value of the method, patients with a normal fasting and/or 120-min serum insulin level at gestation week < or = 16 should undergo an OGTT only at gestation weeks 32-34.