Persistent Glucose Intolerance Research Articles

Glucokinase maturity-onset diabetes of the young as a mimicker of stress hyperglycemia: a case report

Febrile seizures are frequently accompanied by stress-induced hyperglycemia. Herein, we report the case of a 1.5-yr-old girl with hyperglycemia during febrile seizures who was subsequently diagnosed with glucokinase (GCK) maturity-onset diabetes of the young (MODY), considering its distinction from stress hyperglycemia. Following the development of febrile seizures owing to adenovirus infection, the patient presented a casual blood glucose level was 185 mg/dL. She had a multigenerational family history of diabetes and a hemoglobin A1c (HbA1c) level of 6.4%. Owing to the persistent glucose intolerance until the age of 5 years, genetic testing was performed, which revealed a heterozygous mutation in GCK, and the patient was diagnosed with GCK-MODY. Precise diagnosis of GCK-MODY individuals is important to avoid administering unnecessary antidiabetic medications. Even during hyperglycemia under stress, multigenerational diabetes and mildly elevated HbA1c levels can suggest GCK-MODY.

Long-Term Effects of Maternal Low-Protein Diet and Post-weaning High-Fat Feeding on Glucose Metabolism and Hypothalamic POMC Promoter Methylation in Offspring Mice.

Substantial evidence indicated that maternal malnutrition could increase the susceptibility to obesity, insulin resistance, and type 2 diabetes in adulthood. It is increasingly apparent that the brain, especially the hypothalamus, plays a critical role in glucose homeostasis. However, little information is known about the mechanisms linking maternal protein restriction combined with post-weaning high-fat (HF) feeding with altered expression of brain neurotransmitters, and investigations into the epigenetic modifications of hypothalamus in offspring have not been fully elucidated. Our objective was to explore the effects of maternal protein restriction combined with post-weaning HF feeding on glucose metabolism and hypothalamic POMC methylation in male offspring mice. C57/BL6 mice were fed on either low-protein (LP) or normal chow (NC) diet throughout gestation and lactation. Then, the male offspring were randomly weaned to either NC or high-fat (HF) diet until 32 weeks of age. Gene expressions and DNA methylation of hypothalamic proopiomelanocortin (POMC) and melanocortin receptor 4 (MC4R) were determined in male offspring. The results showed that birth weights and body weights at weaning were both significantly lower in male offspring mice of the dams fed with a LP diet. Maternal protein restriction combined with post-weaning high-fat feeding, predisposes higher body weight, persistent glucose intolerance (from weaning to 32 weeks of age), hyperinsulinemia, and hyperleptinemia in male offspring mice. POMC and MC4R expressions were significantly increased in offspring mice fed with maternal LP and postnatal high-fat diet (P < 0.05). Furthermore, maternal protein restriction combined with post-weaning high-fat feeding induced hypomethylation of POMC promoter in the hypothalamus (P < 0.05) and POMC-specific methylation (%) was negatively correlated with the glucose response to a glucose load in male offspring mice (r = −0.42, P = 0.039). In conclusion, maternal LP diet combined with post-weaning high-fat feeding predisposed the male offspring to impaired glucose metabolism and hypothalamic POMC hypomethylation. These findings can advance our thinking about hypothalamic POMC gene methylation between maternal LP diet combined with post-weaning high-fat feeding and metabolic health in offspring.

Metformin enhances protection in guinea pigs chronically infected with Mycobacterium tuberculosis

Tuberculosis (TB) is a chronic inflammatory disease that is often associated with alterations in systemic and cellular metabolism that resolves following successful antimicrobial drug treatment. We hypothesized that altered systemic glucose metabolism as a consequence of Mycobacterium tuberculosis (Mtb) infection, contributes to TB pathogenesis, and when normalized with anti-glycemic drugs would improve clinical outcomes. To test this hypothesis, guinea pigs were treated daily with the anti-diabetic drug metformin starting 4 weeks prior or concurrent with aerosol exposure to the H37Rv strain of Mtb. In the chronic stages of infection, Mtb infected metformin-treated animals had restored systemic insulin sensitivity but remained glucose intolerant as determined by oral glucose tolerance testing. Despite persistent glucose intolerance, metformin-treated guinea pigs had a 2.8-fold reduction in lung lesion burden and a 0.7 log decrease in CFUs. An alternative hypothesis that metformin treatment improved clinical disease by having a direct effect on immune cell energy metabolism was tested using extracellular flux analysis and flow cytometry. The proinflammatory immune response to Mtb infection in untreated guinea pigs was associated with a marked increase in energy metabolism (glycolysis and mitochondrial respiration) of peripheral blood mononuclear cells (PBMCs), which was normalized in metformin-treated guinea pigs. Moreover, both CD4+ and CD8+ T lymphocytes from Mtb infected, metformin treated animals maintained a more normal mitochondrial membrane potential while those isolated from untreated animals had persistent mitochondrial hyperpolarization. These data suggest that metformin promotes natural host resistance to Mtb infection by maintaining immune cell metabolic homeostasis and function during the chronic stages of active TB disease.

Rapid and Concomitant Gut Microbiota and Endocannabinoidome Response to Diet-Induced Obesity in Mice.

The intestinal microbiota and the expanded endocannabinoid (eCB) system, or endocannabinoidome (eCBome), have both been implicated in diet-induced obesity and dysmetabolism. These systems were recently suggested to interact during the development of obesity. We aimed at identifying the potential interactions between gut microbiota composition and the eCBome during the establishment of diet-induced obesity and metabolic complications. Male mice were fed a high-fat, high-sucrose (HFHS) diet for 56 days to assess jejunum, ileum, and cecum microbiomes by 16S rRNA gene metataxonomics as well as ileum and plasma eCBome by targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS). The HFHS diet induced early (3 days) and persistent glucose intolerance followed by weight gain and hyperinsulinemia. Concomitantly, it induced the elevation of the two eCBs, anandamide, in both ileum and plasma, and 2-arachidonoyl-glycerol, in plasma, as well as alterations in several other N-acylethanolamines and 2-acylglycerols. It also promoted segment-specific changes in the relative abundance of several genera in intestinal microbiota, some of which were observed as early as 3 days following HFHS diet. Weight-independent correlations were found between the relative abundances of, among others, Barnesiella, Eubacterium, Adlercreutzia, Parasutterella, Propionibacterium, Enterococcus, and Methylobacterium and the concentrations of anandamide and the anti-inflammatory eCBome mediator N-docosahexaenoyl-ethanolamine. This study highlights for the first time the existence of potential interactions between the eCBome, an endogenous system of multifunctional signaling lipids, and several intestinal genera during early and late HFHS-induced dysmetabolic events, with potential impact on the host capability of adapting to increased intake of fat and sucrose.IMPORTANCE The intestinal microbiota and the expanded endocannabinoid system, or endocannabinoidome, have both been implicated in diet-induced obesity and dysmetabolism. This study aims at identifying the potential interactions between these two fundamental systems-which form the gut microbiota-endocannabinoidome axis-and their involvement in the establishment of diet-induced obesity and related metabolic complications. We report here time- and segment-specific microbiome disturbances as well as modifications of intestinal and circulating endocannabinoidome mediators during high-fat, high-sucrose diet-induced glucose intolerance and subsequent obesity and hyperinsulinemia. This highlights the involvement of, and the interaction between, the gut microbiota and the endocannabinoidome during metabolic adaptation to high-fat and high-sucrose feeding. These results will help identifying actionable gut microbiome members and/or endocannabinoidome mediators to improve metabolic health.

Incident Diabetes in Survivors of Critical Illness and Mechanisms Underlying Persistent Glucose Intolerance: A Prospective Cohort Study.

Stress hyperglycemia occurs in critically ill patients and may be a risk factor for subsequent diabetes. The aims of this study were to determine incident diabetes and prevalent prediabetes in survivors of critical illness experiencing stress hyperglycemia and to explore underlying mechanisms. This was a prospective, single center, cohort study. At admission to ICU, hemoglobin A1c was measured in eligible patients. Participants returned at 3 and 12 months after ICU admission and underwent hemoglobin A1c testing and an oral glucose tolerance test. Blood was also collected for hormone concentrations, whereas gastric emptying was measured via an isotope breath test. β-cell function was modeled using standard techniques. Tertiary-referral, mixed medical-surgical ICU. Consecutively admitted patients who developed stress hyperglycemia and survived to hospital discharge were eligible. Consent was obtained from 40 patients (mean age, 58 yr [SD, 10], hemoglobin A1c 36.8 mmol/mol [4.9 mmol/mol]) with 35 attending the 3-month and 26 the 12-month visits. At 3 months, 13 (37%) had diabetes and 15 (43%) had prediabetes. At 12 months, seven (27%) participants had diabetes, whereas 11 (42%) had prediabetes. Mean hemoglobin A1c increased from baseline during the study: +0.7 mmol/mol (-1.2 to 2.5 mmol/mol) at 3 months and +3.3 mmol/mol (0.98-5.59 mmol/mol) at 12 months (p = 0.02). Gastric emptying was not significantly different across groups at either 3 or 12 months. Diabetes and prediabetes occur frequently in survivors of ICU experiencing stress hyperglycemia. Based on the occurrence rate observed in this cohort, structured screening and intervention programs appear warranted.

Viral Infection “Interferes” with Glucose Tolerance

In this issue of Immunity, Šestan etal. (2018) show that viral-induced inflammation leads to insulin resistance in skeletal muscle, followed by compensatory hyperinsulinemia, which promotes the anti-viral effector response of CD8+ Tcells. Interestingly, this leads to persistent glucose intolerance and the progression of type 2 diabetes in pre-diabetic animals.

Ovine prenatal growth restriction impacts glucose metabolism and body composition throughout life in both sexes.

Low birthweight is a risk factor for later adverse health. Here the impact of placentally mediated prenatal growth restriction followed by postnatal nutrient abundance on growth, glucose metabolism and body composition was assessed in both sexes at key stages from birth to mid-adult life. Singleton-bearing adolescent dams were fed control or high nutrient intakes to induce normal or growth-restricted pregnancies respectively. Restricted lambs had ~40% reduced birthweight. Fractional growth rates were higher in restricted lambs of both sexes predominantly during suckling/juvenile phases. Thereafter, rates and patterns of growth differed by sex. Absolute catch-up was not achieved and restricted offspring had modestly reduced weight and stature at mid-adulthood necropsy (~109 weeks). Dual-energy X-ray absorptiometry revealed lower bone mineral density in restricted vs normal lambs at 11, 41, 64 and 107 weeks, with males > females from 41 weeks onwards. Body fat percentage was higher in females vs males throughout, in restricted vs normal lambs at weaning (both sexes) and in restricted vs normal females at mid-adulthood. Insulin secretion after glucose challenge was greater in restricted vs normal of both sexes at 7 weeks and in restricted males at 32 weeks. In both sexes, fasting glucose concentrations were greater in restricted offspring across the life course, while glucose area under the curve after challenge was higher in restricted offspring at 32, 60, 85 and 106 weeks, indicative of persistent glucose intolerance. Therefore, prenatal growth restriction has negative consequences for body composition and metabolism throughout the life course with the effects modulated by sex differences in postnatal growth rates, fat deposition and bone mass accrual.

Predicting persistent impaired glucose tolerance in patients with gestational diabetes: The role of high sensitivity CRP and adiponectin.

To evaluate whether maternal serum adiponectin and high-sensitivity C-reactive protein (hsCRP) levels at the time of gestational diabetes mellitus (GDM) diagnosis are associated with persistent glucose intolerance in GDM women at 6 to 12weeks postpartum. This is a secondary analysis of prospective randomized trial of GDM women enrolled in a behaviour education programme. Women with a GDM diagnosis ≥20weeks were included. At the time of randomization, serum adiponectin and hsCRP levels were drawn. After delivery, women underwent a 2-hour 75-g oral glucose tolerance test at 6 to 12weeks postpartum. Persistent impaired glucose tolerance (P-IGT) was defined as impaired fasting glucose, impaired glucose tolerance, or a diagnosis of type 2 diabetes mellitus. Regression models and receiver operator curves were used to evaluate the association between midpregnancy adiponectin and hsCRP and persistent impaired glucose tolerance. Of 100 women in the trial, 63 completed postpartum glucose testing. Twenty (31.7%) of the women had P-IGT. Median hsCRP levels were higher at randomization (22-34wk) in women with persistent impaired glucose tolerance compared with women with normal glucose tolerance (5.1 vs 3.8, P=.01). After adjustment for the original study intervention, the association between hsCRP and P-IGT persisted (odds ratio, 3.45; 95% confidence interval, 1.34-8.92; P=.01) and had good diagnostic performance with an area under the curve of 0.73. There was no difference in median adiponectin levels between groups (44.8 vs 52.0, P=.57) or in odds of P-IGT (odds ratio, 0.81; 95% confidence interval, 0.33-1.99; P=.65), and area under the curve=0.54. Midpregnancy high sensitivity CRP is a potential predictor of persistent impaired glucose tolerance diagnosed on the postpartum 2-hour 75-g oral glucose tolerance test in GDM women in the immediate postpartum period. Further investigation is needed in a larger population of women prior to using specific cut-offs for diagnostic purposes. High-sensitivity C-reactive protein levels in the immediate postpartum period should be seen as an adjunct, not a replacement, for the standard long-term screening of women with a history of a GDM pregnancy.

Routine exercise ameliorates the metabolic side-effects of treatment with the atypical antipsychotic drug olanzapine in rats

Second generation antipsychotic (SGA) drugs are effective treatments for psychosis. Common side-effects of SGAs include metabolic dysregulation and risk of cardiometabolic disorders. Metabolic side-effects, including glucose intolerance, can be accurately modelled in rodents. The benefits of interventions used for treating metabolic side-effects of SGAs are mostly unknown. In a 9wk longitudinal study, female rats were given daily olanzapine (10mg/kg s.c.) or vehicle. Animals were either sedentary or allowed 1 or 3h daily access to a running wheel, with total wheel revolutions electronically quantified to reflect exercise intensity. Glucose tolerance tests were performed once weekly to measure glycemic control. Drug levels were measured at week 4. At week 9, abdominal fat and skeletal muscle levels of Glucose Transporter 4 (GLUT4) were measured. Exercise intensity progressively increased over time in all groups given access to running wheels; however, rats treated with olanzapine consistently exercised less than those given the vehicle. Olanzapine caused acute and persistent glucose intolerance throughout the study, which was markedly, though incompletely, ameliorated by exercise. Exercise did not affect glycemic regulation in vehicle-treated rats. Olanzapine-treated rats showed greater central adiposity. Levels of GLUT4 in skeletal muscle were higher in both groups of exercising than in sedentary rats, and GLUT4 values were negatively correlated with glucose intolerance. Routine exercise reduced olanzapine-induced glucose intolerance and increased skeletal muscle levels of GLUT 4, the insulin-responsive transporter that mediates glucose uptake into cells. The current animal model is suitable for evaluating physiological pathways involved with glucose intolerance.

Postpartum Diabetes Testing Among Women with Recent Gestational Diabetes Mellitus: PRAMS 2009–2010

The objective of this study was to estimate rates of and factors associated with postpartum diabetes testing in women with recent gestational diabetes mellitus (GDM). Secondary data analysis was conducted using data from the 2009 and 2010 Pregnancy Risk Assessment Monitoring System from three states and one city (Colorado, Minnesota, Utah, and New York City). Frequency of postpartum diabetes testing was estimated overall and among women who attended a postpartum visit. Multivariable logistic regression was used to determine factors associated with postpartum diabetes testing. Approximately 8.2% [95% confidence interval (CI) 7.5-8.9] of women self-reported a history of GDM (n = 829), of which 48.5% (43.9-53.1) reported being tested for diabetes postpartum. Among the 90.0% (86.5-93.4) of women with recent GDM who attended the postpartum visit, 51.7% (46.1-57.2) reported being tested for diabetes postpartum. Women who received inadequate/intermediate prenatal care were half as likely to report postpartum testing compared with women who received adequate prenatal care [odds ratio 0.45 (95% CI 0.25-0.83)]. Women with a prepregnancy body mass index classified as obese were over twice as likely to report postpartum testing compared to normal weight women. Women with GDM are at increased risk of persistent glucose intolerance after delivery, yet postpartum testing rates remain around 50%, regardless of attendance to the postpartum visit. Improving adequacy of prenatal care might further increase postpartum testing rates. Continued efforts to translate postpartum testing into practice are needed among these women at risk for future type 2 diabetes.

Exercise training in the aerobic/anaerobic metabolic transition prevents glucose intolerance in alloxan-treated rats

BackgroundNinety percent of cases of diabetes are of the slowly evolving non-insulin-dependent type, or Type 2 diabetes. Lack of exercise is regarded as one of the main causes of this disorder. In this study we analyzed the effects of physical exercise on glucose homeostasis in adult rats with type 2 diabetes induced by a neonatal injection of alloxan.MethodsFemale Wistar rats aged 6 days were injected with either 250 mg/kg of body weight of alloxan or citrate buffer 0.01 M (controls). After weaning, half of the animals in each group were subjected to physical training adjusted to meet the aerobic-anaerobic metabolic transition by swimming 1 h/day for 5 days a week with weight overloads. The necessary overload used was set and periodically readjusted for each rat through effort tests based on the maximal lactate steady state procedure. When aged 28, 60, 90, and 120 days, the rats underwent glucose tolerance tests (GTT) and their peripheral insulin sensitivity was evaluated using the HOMA index.ResultsThe area under the serum glucose curve obtained through GTT was always higher in alloxan-treated animals than in controls. A decrease in this area was observed in trained alloxan-treated rats at 90 and 120 days old compared with non-trained animals. At 90 days old the trained controls showed lower HOMA indices than the non-trained controls.ConclusionNeonatal administration of alloxan induced a persistent glucose intolerance in all injected rats, which was successfully counteracted by physical training in the aerobic/anaerobic metabolic transition.

Swimming Training at Aerobic/Anaerobic Metabolic Transition Prevents Glucose Homeostasis Disturbances in Neonatal Alloxan Treated Rats

PURPOSE: The present study aimed to analyze the effects of physical exercise performed on the aerobic/anaerobic metabolic transition intensity on the glucose homeostasis of adult rats subjected to neonatal administration of alloxan, on experimental model of type 2 diabetes. METHODS: Female newborn Wistar rats (6 days old) received Alloxan (250mg/ Kg body weight), intraperitoneally (alloxan group); or vehicle citrate buffer (0,01M) (control group). After weaning (28 days), the animals were subdivided in to 4 groups: control (C); trained control (TC); Alloxan (A) and trained Alloxan (TA). Trained animals were submitted to swimming, 1 h/day, 5 days/week, supporting an overload equivalent to the aerobic/anaerobic metabolic transition. Before the training, all the animals performed to an effort test for identification of the aerobic/anaerobic metabolic transition using the maximal lactate steady state procedure. At 28, 60, 90 and 120 days old, the animals were subjected to glucose tolerance test (GTTo), analyzed by the total area under curve of the serum glucose (mmol/L x 120 min.). RESULTS: When GTTo was carried out at 28 days, the area under the serum glucose curve increased in the rats which received alloxan neonatally (A= 1309.0 ± 337.8*) when compared to control group (C= 817.6 ± 59.5). At 60 days old, alloxan and trained alloxan animals kept high serum glucose concentrations when compared to the control animals (C: 774.9 ± 69.0; A: 1043.4 ± 103.1*; TC: 756.9 ± 38.9; and TA: 1131.2 ± 189.7*, p<0.05 ANOVA). At 90 (C: 735.9 ± 64.1; A: 1162.9 ± 202.9; TC: 670.9 ± 40.8; and TA: 1017.4 ± 129.0* p<0.05 ANOVA ) and 120 days old (C:755.8 ± 645; A: 1299.4 ± 198.3; TC:640.7± 106.4; and TA: 972.2 ± 135.0 *, p<0.05 ANOVA) however, the area under the serum glucose curve decreased in the trained alloxan animals when compared with the Alloxan group. CONCLUSIONS: The neonatal administration of alloxan induced persistent glucose intolerance. On the other hand, physical training at the aerobic/anaerobic metabolic transition prevented the glucose homeostasis disturbance in the alloxan treated rats. Supported by FAPESP (proc. 06/51213-0)

The effect of glycemic control on heart failure severity in diabetics

Introduction: Glycosylated hemoglobin (Hb A1c) is an index of metabolic control in diabetes (D). Recent studies suggest that poor glycemic control in diabetic patients (pts) indicated by elevated Hb A1c levels (>7.0%) may be associated with increased risk of heart failure (HF). Our goal was to investigate the association between Hb A1c level and severity of HF in advanced HF pts with D. Methods: Among 180 pts referred for cardiac transplantation, 35 consecutive patients with advanced HF and D underwent evaluation with serum glucose, serum creatinine, Hb A1c, B-type natriuretic peptide (BNP), cardiopulmonary exercise testing and right heart catheterizaton. Pts were divided into two groups based on Hb A1c7% (Group A, mean Hb A1c=5.9±0.8) and Hb A1c >7% (Group B, mean Hb A1c=10.1±2.4). Results:∗Parameter (mean value)Hb A1c ≤7% (Group A: n=19)Hb A1c >7% (Group B: n=16)p valueAge (years)53.9±13.149.6±13.30.34Gender (male %)79690.70NYHA Class2.9±0.83.9±0.90.43Peak Oxygen Consumption (V02) ml/kg/minute16.2±2.214.5±3.40.25BNP (pg/ml)399.6±281.1754.8±696.40.05∗Pulmonary capillary wedge (PCW) pressure (mm Hg)22.2±8.026.2±8.50.24Glucose (mg/dl)141±75217±1190.03∗Creatinine (mg/dl)1.4±0.51.4±0.40.88BMI26.5±7.927.9±6.30.57% on Insulin9130.09∗p ≤ 0.05 Conclusion: BNP level was significantly elevated in diabetic pts with Hb A1c >7% (Group B). Glucose level was significantly higher in Group B. In Group B pts compared to Group A there was also a trend towards increased severity of symptoms demonstrated by worse NYHA class, lower peak VO2 and higher PCW pressure. Poor glycemic control in HF pts appears to have negative impact on functional capacity and severity of symptoms. Persistent glucose intolerance as shown by elevated Hb A1c>7% may be contributing to increased fluid retention reflected by higher PCW pressure and significantly higher BNP level in Group B compared to Group A pts. The effect of improved glycemic control on clinical outcomes such as frequency of hospitalization and survival in advanced HF pts with D deserves further study.

Gestational diabetes mellitus in Korea: prevalence and prediction of glucose intolerance at early postpartum

To determine the prevalence of glucose intolerance in Korean women with gestational diabetes mellitus (GDM) between 6 and 8 weeks postpartum and identify which antepartum variables were predictive of postpartum diabetes and impaired glucose tolerance (IGT), we prospectively performed 75 g oral glucose tolerance test (OGTT) between 6 and 8 weeks postpartum in women with GDM. WHO criteria were used for classification of glucose tolerance postpartum. Of 392 women with GDM were detected during the study period, 311 women participated in this study. Of the 311 participants, 119 (38.3%) women were found to have persistent glucose intolerance; 47 (15.1%) had diabetes and 72 (23.2%) had IGT. The prevalence of postpartum IGT and diabetes increased in parallel with the metabolic severity during pregnancy. Multiple logistic regression analysis revealed that pre-pregnancy weight, gestational age at diagnosis of GDM, 2-h glucose and 3-h insulin concentrations of diagnostic OGTT were independently associated with postpartum diabetes. Pre-pregnancy weight, 2-h glucose and 1-h insulin concentrations were independently associated with postpartum IGT. Our results support the importance of postpartum testing in Korean women with GDM, and demonstrated that impaired β-cell function and pre-pregnancy obesity were associated with glucose intolerance at early postpartum.

Maternal ante-natal parameters as predictors of persistent postnatal glucose intolerance: a comparative study between Afro-Caribbeans, Asians and Caucasians.

To measure the prevalence of persistent glucose intolerance at 6-12 weeks postpartum in various ethnic groups to assess the value of targeted postpartum screening. A retrospective study was performed using computerized databases from two large maternity units within one UK region. Both units used the same screening strategy for gestational diabetes mellitus (GDM) and the same postpartum follow-up at 6-12 weeks using a 75-g oral glucose tolerance test (OGTT). A total of 221 women with a diagnosis of GDM/impaired glucose tolerance (IGT) in the index pregnancy in addition to a completed postpartum 75-g OGTT were studied. Of these, 91 were Caucasian, 89 were of Indo-Asian (Asian) origin and 41 were of Afro-Caribbean origin. The study showed that 35% Indo-Asians had persistent postpartum glucose intolerance compared with 7% Caucasians and 5% Afro-Caribbeans (P < 0.003). Insulin requirement during pregnancy and a diagnosis of gestational diabetes prior to 20 weeks of pregnancy were predictive for persistent postpartum glucose intolerance amongst Indo-Asians. The frequency of postpartum glucose intolerance among Indo-Asian women is significantly greater than among age-matched Caucasian and Afro-Caribbean women. We suggest that all Indo-Asian women with gestational diabetes should undergo postpartum screening for persistent glucose intolerance. However, in non-Asian women selective screening may be more cost effective.

Role of endogenous glucagon-like peptide-1 in islet regeneration after partial pancreatectomy.

A reduction in beta-cell mass is an important causative factor in type 1 and type 2 diabetes. Glucagon-like peptide-1 (GLP-1) and the long-acting agonist exendin 4 (Ex-4) expand beta-cell mass by stimulating neogenesis and proliferation. In the partial pancreatectomy (Ppx) model, exogenous Ex-4 promotes islet regeneration, leading to sustained improvement in glucose tolerance. In this study, we investigate the potential role of endogenous GLP-1 in islet growth. We examined beta-cell mass regeneration after 70% Ppx in mice receiving the GLP-1 antagonist Ex9-39 and in GLP-1R(-/-) mice. In Ex9-39-treated sham-operated mice, persistent fasting hyperglycemia was observed, but beta-cell mass was not diminished. In pancreatectomized mice, persistent glucose intolerance was noted, but this was not further exacerbated by Ex9-39. Accordingly, beta-cell mass recovery of Ppx mice was not impaired by Ex9-39. In contrast, GLP-1R(-/-) CD1 mice showed worse glucose intolerance after Ppx compared with wild-type CD1 Ppx mice, and this correlated with a significant defect in beta-cell mass regeneration. The recovery of beta-cell mass differed markedly in the BALB/c and CD1 control mice, indicating a significant role of genetic background in the regulation of beta-cell mass. These studies point to a role for endogenous GLP-1 in beta-cell regeneration after Ppx in mice.

Risk factors for persistent glucose intolerance in women with gestational diabetes

Risk factors for persistent glucose intolerance in women with gestational diabetes

Meeting the challenge of neonatal hyperglycemia.

LBW and VLBW neonates have presented neonatal caregivers with a unique challenge to meet their nutritional and growth needs. Unfortunately, the neonate's immature physiologic function may lead to persistent glucose intolerance and a nonresponsiveness to endogenous insulin. The use of insulin infusions for the treatment of hyperglycemia may support normoglycemia and improve nutritional supplementation.

Natural history of incidental hyperglycemia and glycosuria of childhood

We prospectively followed 29 children and adolescents over a 1- to 8-year period who were referred for evaluation of hyperglycemia (in the absence of diabetes) or glycosuria found on routine screening or during acute illness. On initial examination, four subjects had islet cell autoantibodies, 4 of 22 had an abnormal intravenous glucose tolerance test result, 6 of 22 had low first-phase insulin release on intravenous glucose tolerance testing, and 10 of 20 had impaired glucose tolerance on oral glucose tolerance testing. On follow-up, insulin-dependent diabetes had developed in two of the four subjects with islet cell autoantibodies. The other two subjects with islet cell antibodies have had persistently abnormal glucose tolerance on both oral and intravenous glucose tolerance testing and have low first-phase insulin responses. Diabetes has developed in none of 25 subjects without islet cell antibodies, although two have persistently abnormal glucose tolerance or insulinopenia. All five subjects with islet cell antibodies or human leukocyte antigen DR3/DR4 with initial impaired glucose tolerance have either acquired diabetes or have abnormal glucose tolerance. In contrast, only one of five subjects with initial impaired glucose tolerance but lacking these markers has persistent glucose intolerance. We conclude that in the absence of islet cell antibodies or human leukocyte antigen DR3/DR4 heterozygosity, incidental hyperglycemia or glycosuria is unlikely to be associated with progression or diabetes.

Factors predicting the course of diabetes mellitus in hyperthyroid patients.

The relationship between changes in glucose tolerance with treatment of hyperthyroidism and various factors that might be relevant to carbohydrate metabolism were investigated in 64 hyperthyroid patients with abnormal glucose tolerance, including 35 cases with fasting plasma glucose (FPG) levels of 140 mg/dl or more. All patients had diffuse toxic goiter. After correction of the hyperthyroidism, glucose intolerance improved in almost all cases, even in cases with fasting hyperglycemia, but diabetes mellitus in patients with FPG above 140 mg/dl and/or delta IRI/delta PG X 30' during a 50-g oral glucose tolerance test below 0.10, persisted. Patients who showed diabetic glucose tolerance even after remission from thyroid dysfunction had significantly lower delta IRI/delta PG X 30' values and a higher incidence of family histories of diabetes mellitus than those not showing diabetic glucose tolerance. There were no significant differences in serum T3 and T4 levels between these two groups of patients. The findings suggest that predisposition to diabetes may be an important factor in persistent glucose intolerance in the hyperthyroidism of Graves' disease. The FPG and delta IRI/delta PG X 30' values may be useful in predicting which patients with hyperthyroidism will have permanent diabetes.