Severity Of Glucose Intolerance Research Articles

274-OR: Beta-Cell Dysfunction Is Associated with Impaired Insulin-Mediated Suppression of Glucagon in Obese Hispanic Americans

Recent studies have demonstrated an increase in the glucagon:insulin ratio in lean versus obese subjects. We assessed insulin-mediated suppression of plasma glucagon levels in 260 obese Hispanic Americans (59 NGT, HbA1c= 5.1±0.1%, BMI= 32.6±0.7; 109 Prediabetes, HbA1c= 5.8±0.1%, BMI= 33.8±0.5; 92 T2D, HbA1c= 7.3±0.2%, BMI= 34±0.5) with varying glucose tolerance. Subjects participated in a 2-h OGTT with measurement of plasma glucose, insulin, glucagon concentrations. During the OGTT, we quantitated insulin-mediated suppression of plasma glucagon concentration, Matsuda Index of insulin sensitivity, and the insulin secretion/insulin sensitivity (disposition) index using plasma C-peptide concentration. There was no difference in fasting plasma glucagon level between obese subjects with normal glucose tolerance (NGT), prediabetes, and type 2 diabetes (T2D). However, there was a progressive decrease in fasting glucagon:insulin ratio from NGT to prediabetes to T2D (8.71±0.72 vs. 6.92±0.53 vs. 5.66±0.41, P<0.01). During OGTT at 60 min, glucagon:insulin ratio increased from NGT to T2D (0.93±0.09 vs. 0.89±0.07 vs. 2.33±0.20, P<0.001), and the suppression of plasma glucagon (compared to basal value) was markedly decreased (10.3±3.4% vs. 9.3±1.9% vs. 2.5±2.8%, P<0.05). At 120 min (OGTT), glucagon:insulin ratio was increased in T2D versus NGT (1.28±0.17 vs. 2.0±0.20, P<0.01). The glucagon:insulin ratio was closely correlated with whole body insulin sensitivity and β-cell function during the fasting state (Matsuda Index, r= 0.51, P<0.001; Disposition Index, r= 0.30, P<0.001) and with Disposition Index during the OGTT at 60 and 120 min (r= -0.41, P<0.001; r= -0.21, P<0.01), respectively. Collectively, these findings indicate that insulin-mediated suppression of glucagon secretion is impaired with increasing severity of glucose intolerance in obese Hispanic Americans and is closely associated with insulin resistance and β-cell dysfunction. Disclosure X. Chen: None. E.R. Maldonado Corchado: None. A. Merovci: None. E. Case: None. D. Tripathy: None. R.A. DeFronzo: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc.

Relationship between threatened miscarriage and gestational diabetes mellitus

BackgroundBoth threatened miscarriage and gestational diabetes mellitus (GDM) are common complications of pregnancy. However, only one pilot study has reported that these complications are not related. We aimed to investigate whether threatened miscarriage is one of the risk factors of GDM.MethodsAn unmatched case-control study of 1567 pregnant Korean women who underwent a two-step approach to diagnose GDM was retrospectively conducted. The eligible women were classified into normal (n = 840), borderline GDM (n = 480), and GDM (n = 247) groups. We analyzed the associations with threatened miscarriage in all groups with adjustment for confounding factors.ResultsThe proportion of women who experienced threatened miscarriage was significantly lower in the GDM group than in the normal group (adjusted odds ratio (OR), 0.38; 95% confidence interval (CI), 0.18–0.78). It was significantly lower in the maternal hyperglycemia group (borderline GDM and GDM groups) than in the normal group (adjusted OR, 0.66; 95% CI, 0.47–0.91). The proportion of women who experienced threatened miscarriage was also significantly lower in the GDM group than in the normal (adjusted OR, 0.35; 95% CI, 0.17–0.70) and borderline GDM groups (adjusted OR, 0.46; 95% CI, 0.22–0.94). Moreover, the proportion of women who experienced threatened miscarriage significantly decreased according to the severity of glucose intolerance (adjusted OR, 0.94; 95% CI, 0.76–1.16).ConclusionThis study demonstrates that threatened miscarriage is associated with decreased risk of GDM and the severity of glucose intolerance in Korean women. Additional studies are warranted to understand the pathophysiologic mechanisms that might exist between these frequent complications of pregnancy.

Periodontal dysbiosis linked to periodontitis is associated with cardiometabolic adaptation to high-fat diet in mice.

Periodontitis and type 2 diabetes are connected pandemic diseases, and both are risk factors for cardiovascular complications. Nevertheless, the molecular factors relating these two chronic pathologies are poorly understood. We have shown that, in response to a long-term fat-enriched diet, mice present particular gut microbiota profiles related to three metabolic phenotypes: diabetic-resistant (DR), intermediate (Inter), and diabetic-sensitive (DS). Moreover, many studies suggest that a dysbiosis of periodontal microbiota could be associated with the incidence of metabolic and cardiac diseases. We investigated whether periodontitis together with the periodontal microbiota may also be associated with these different cardiometabolic phenotypes. We report that the severity of glucose intolerance is related to the severity of periodontitis and cardiac disorders. In detail, alveolar bone loss was more accentuated in DS than Inter, DR, and normal chow-fed mice. Molecular markers of periodontal inflammation, such as TNF-α and plasminogen activator inhibitor-1 mRNA levels, correlated positively with both alveolar bone loss and glycemic index. Furthermore, the periodontal microbiota of DR mice was dominated by the Streptococcaceae family of the phylum Firmicutes, whereas the periodontal microbiota of DS mice was characterized by increased Porphyromonadaceae and Prevotellaceae families. Moreover, in DS mice the periodontal microbiota was indicated by an abundance of the genera Prevotella and Tannerella, which are major periodontal pathogens. PICRUSt analysis of the periodontal microbiome highlighted that prenyltransferase pathways follow the cardiometabolic adaptation to a high-fat diet. Finally, DS mice displayed a worse cardiac phenotype, percentage of fractional shortening, heart rhythm, and left ventricle weight-to-tibia length ratio than Inter and DR mice. Together, our data show that periodontitis combined with particular periodontal microbiota and microbiome is associated with metabolic adaptation to a high-fat diet related to the severity of cardiometabolic alteration.

The components of metabolic syndrome in women

The components of metabolic syndrome in women

Bone-specific insulin resistance disrupts whole-body glucose homeostasis via decreased osteocalcin activation

Insulin signaling in osteoblasts has been shown recently to contribute to whole-body glucose homeostasis in animals fed a normal diet; however, it is unknown whether bone contributes to the insulin resistance that develops in animals challenged by a high-fat diet (HFD). Here, we evaluated the consequences of osteoblast-specific overexpression of or loss of insulin receptor in HFD-fed mice. We determined that the severity of glucose intolerance and insulin resistance that mice develop when fed a HFD is in part a consequence of osteoblast-dependent insulin resistance. Insulin resistance in osteoblasts led to a decrease in circulating levels of the active form of osteocalcin, thereby decreasing insulin sensitivity in skeletal muscle. Insulin resistance developed in osteoblasts as the result of increased levels of free saturated fatty acids, which promote insulin receptor ubiquitination and subsequent degradation. Together, these results underscore the involvement of bone, among other tissues, in the disruption of whole-body glucose homeostasis resulting from a HFD and the involvement of insulin and osteocalcin cross-talk in glucose intolerance. Furthermore, our data indicate that insulin resistance develops in bone as the result of lipotoxicity-associated loss of insulin receptors.

High urinary ACE2 concentrations are associated with severity of glucose intolerance and microalbuminuria

Angiotensin-converting enzyme 2 (ACE2) plays an important role in glucose metabolism and renal function. However, the relationship between ACE2 and hyperglycemia or microalbuminuria has not been established in humans. We investigated whether urinary ACE2 levels are associated with abnormal glucose homeostasis and urinary albumin excretion. We developed an ELISA for quantifying ACE2 in urine. The ELISA was used to measure urinary ACE2 levels in 621 subjects with: normal glucose tolerance (NGT; n=77); impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) (n=132); and type 2 diabetes mellitus (T2DM, n=412). Insulin resistance was assessed by homeostasis model assessment for insulin resistance (HOMA-IR) index and urinary albumin excretion by urine albumin-to-creatinine ratio (ACR). Other biochemical and anthropometric parameters were measured. Urinary ACE2 levels were significantly higher in insulin-resistant subjects with IFG, IGT, and T2DM than in the NGT group (P<0.001). Urinary ACE2 concentrations appeared to correlate with HOMA-IR, fasting blood glucose, triglyceride, high-sensitivity C-reactive protein, serum creatinine, urinary ACR, and systolic blood pressure (all P<0.05). After adjustment for impaired renal function and other metabolic parameters, urinary ACE2 concentration was still associated with a higher risk for T2DM (OR 1.80, 95% CI 1.05-3.08, P=0.02). In addition, urinary ACE2 levels were highly predictive of microalbuminuria after adjusting for clinical risk factors (OR 2.68, 95% CI 1.55-4.64, P<0.001). Our data suggest that the urinary ACE2 level is closely associated with T2DM and is an independent risk factor for microalbuminuria.

Beta cell dysfunction and its clinical significance in gestational diabetes

The aim of this study is to explore beta cell dysfunction and its clinical significance in gestational diabetes mellitus (GDM). We assessed insulin sensitivity and insulin secretion in a total of 277 Japanese women between 24 and 27 weeks of pregnancy who underwent a 2 h, 75 g oral glucose tolerance test (OGTT) because of an abnormal result on a 1 h 50 g oral glucose challenge conducted as part of a standard screening for GDM. Insulin sensitivity was evaluated by an insulin sensitivity index derived from OGTT (IS(OGTT)), whereas insulin secretion was calculated as a ratio of the total area under the insulin curve to the total area under the glucose curve (AUC(ins/glu)). Beta cell function in relation to insulin sensitivity (i.e. disposition index) was derived from the product of insulin sensitivity and insulin secretion (i.e. AUC(ins/glu) × IS(OGTT)). In women diagnosed with GDM (n=57), the disposition index was significantly lower than that in those without GDM, irrespective of obesity. The disposition index in women with GDM was significantly correlated with levels of fasting and mean preprandial capillary glucose and HbA1c before initiating insulin therapy (r = -0.45, -0.38, -0.49, respectively). Furthermore, there was a significant correlation between the disposition index and total insulin dosage to achieve glycemic goal (r = -0.41). In conclusion, we demonstrated beta cell dysfunction in Japanese women with GDM irrespective of obesity. The level of beta cell dysfunction in GDM was associated with the severity of glucose intolerance and total insulin dosage required. These findings underpin clinical significance of beta cell dysfunction in GDM.

Are short women at risk for gestational diabetes mellitus?

The aim of the study was to assess the influence of height variations on the risk of gestational diabetes mellitus (GDM). We analyzed the medical records of 1830 Caucasian women with GDM and 1011 healthy pregnant women. The following data were collected: age, prior macrosomia, prior GDM, parity, history of type 2 diabetes in first-degree relatives, weight before pregnancy, weight gain during pregnancy, glucose level at the first obstetric visit, results of the glucose challenge test and oral glucose tolerance test (OGTT), HbA1c, and method for treatment of GDM. Women with GDM were significantly shorter than the healthy controls (165.7+/-5.6 vs 163.8+/-6.6 cm; P<0.001). The differences in height were not significant between GDM women who required insulin therapy and those treated with diet alone (P=0.12). All the studied variables, including height, were independently associated with GDM. Even after adjustment for confounding variables, height was still associated with GDM (odds ratio 0.958, 95% confidence interval: 0.94-0.97; P<0.00001). In women with GDM diagnosed by 75-g OGTT, we found a significant inverse association of height adjusted for age and pregravid weight with 2-h glucose level (beta=-0.12; P<0.0001). Caucasian women with GDM are shorter than pregnant women without GDM regardless of the diagnostic criteria used or the severity of glucose intolerance. Although height is an independent predictor for GDM, its predictive value for identifying women at risk is relatively low and should not be considered in selective screening for this disease.

Adiponectin is independently associated with apolipoprotein B to A-1 ratio in Koreans

Apolipoprotein B to A-1 (apo B/A-1) ratio is reportedly a better predictor of atherosclerotic vascular disease than low-density lipoprotein cholesterol (LDL-C). The aim of this study was to assess the association of serum apo B/A-1 ratio with insulin resistance and adiponectin in patients with different grades of glucose intolerance. Patients were divided according to glucose tolerance into 3 groups: normal glucose tolerance without metabolic syndrome (n = 229), impaired fasting glucose (subjects with fasting plasma glucose level between 100 and 125 mg/dL, n = 658), and type 2 diabetes mellitus (n = 381). Serum concentrations of apo B, apo A-1, glucose, total cholesterol (TC), triglycerides, and high-density lipoprotein cholesterol (HDL-C) and adiponectin were measured. Insulin resistance was estimated by the homeostasis model assessment of insulin resistance index (HOMA-IR). There were significant differences in metabolic parameters among the groups, including waist circumference, insulin, HOMA-IR, and apo B/A-1 ratio, which increased sequentially with glucose intolerance, whereas adiponectin level decreased with increasing severity of glucose intolerance. The apo B/A-1 ratio was significantly correlated with TC, triglycerides, LDL-C, HDL-C, adiponectin, and HOMA-IR in normal glucose tolerance, impaired fasting glucose, and type 2 diabetes mellitus. Multiple regression analysis showed that apo B/A-1 ratio was significantly associated with TC, LDL-C, HDL-C, and adiponectin. In conclusion, apo B/A-1 ratio was significantly associated with insulin resistance according to glucose intolerance; and serum adiponectin was an important independent factor associated with apo B/A-1 ratio in Koreans.

Serum levels of retinol-binding protein-4 and its association with metabolic syndrome in first-degree relatives of type 2 diabetes mellitus

To evaluate serum levels of retinol-binding protein-4 (RBP-4) in first-degree relatives (FDR) of type 2 diabetes mellitus (T2DM) with different glucose tolerance status and to observe its correlation to metabolic syndrome (MS). Subjects from FDR of T2DM, including 174 with NGT, 55 with IGT/IFG, and 71 patients with newly diagnosed of T2DM and 114 subjects without diabetic family history as control group [(18 +/- 7) microg/ml vs (22 +/- 8) microg/ml, (NC) [(18 +/- 7) microg/ml vs (22 +/- 8) microg/ml, were recruited. Serum RBP-4 level was measured by radioimmunoassay. Insulin resistance was evaluated by the homeostasis model assessment (HOMA-IR). MS was diagnosed according to 2005 IDF consensus. (1) Serum RBP-4 levels in NC, NGT, IFG/IGT and T2DM groups were (18 +/- 7), (22 +/- 8), (24 +/- 9) and (26 +/- 9) microg/ml respectively. Serum RBP-4 was significantly elevated in NGT group of diabetic FDR as compared with NC group [(26 +/- 9) microg/ml vs (24 +/- 9) microg/ml], and increased with the severity of glucose intolerance. However, no difference was found between serum RBP-4 in the IFG/IGT and T2DM groups. (2) When the distribution of RBP-4 was stratified into quartiles (Q1-Q4), subjects in the top quartile (Q4) was not only associated with greater risk for impaired glucose regulation as compared with Q1 OR = 5.26) , but also significantly with risk for hypertension (OR = 1.96), dyslipidemia (OR = 4.14), obesity (OR = 2.18) and MS (OR = 4.30). (1) Serum RBP-4 levels in FDR of T2DM were elevated significantly even before the development of impaired glucose regulation and were further increased with severity of glucose tolerance, suggesting a possible role of RBP-4 in the early pathogenesis of T2DM. (2) Serum RBP-4 level was closely related to MS.

High Plasma Retinol Binding Protein-4 and Low Plasma Adiponectin Concentrations Are Associated with Severity of Glucose Intolerance in Women with Previous Gestational Diabetes Mellitus

Women with previous gestational diabetes mellitus (pGDM) are at high risk of developing type 2 diabetes mellitus in the future. The role of adipokines in women with pGDM has not been established. We investigated whether circulating adipokine concentration is associated with abnormal glucose homeostasis in women with pGDM. DESIGN, SETTING, PATIENTS, AND MAIN OUTCOME MEASURES: We measured the plasma concentrations of retinol-binding protein-4 (RBP4), transthyretin (TTR), and adiponectin and metabolic parameters in four groups of women who exhibited normal glucose tolerance (NGT) during a previous pregnancy (NP, n = 17), NGT after GDM (GDM-NGT, n = 72), impaired glucose tolerance after GDM (GDM-IGT, n = 60), and type 2 diabetes after GDM (GDM-DM, n = 8). Plasma RBP4 concentration was significantly higher in women with GDM-DM, GDM-IGT, and GDM-NGT than in those with NP. RBP4 concentration correlated positively with TTR concentration; fasting plasma glucose, insulin, and triglyceride concentrations; blood pressure; abdominal fat area; and homeostasis model assessment of insulin resistance. Plasma TTR concentration was elevated in women with GDM-DM compared with other groups. In contrast, adiponectin concentration was lowest in the GDM-DM group and correlated inversely with parameters of insulin resistance. Resistin concentration was higher only in the GDM-NGT and GDM-IGT groups, whereas leptin did not differ between groups. Plasma RBP4 and adiponectin concentrations were inversely correlated. The severity of glucose intolerance in women with pGDM is associated with high RBP4 and low adiponectin concentrations.

Abnormal glucose tolerance in cystic fibrosis: Why should patients be screened?

Abnormal glucose tolerance in cystic fibrosis: Why should patients be screened?

Gestational diabetes mellitus

The proposed risks from abnormal glucose tolerance in pregnancy are continuous. Gestational diabetes is thus an arbitrary condition. The risks to the fetus are largely determined by fetal size, and those of the mother by the severity of glucose intolerance. Screening policies vary throughout the world, and all have deficiencies. Policies should be determined locally, as population and organizational issues will influence efficacy. Clinicians need to agree diagnostic criteria as minor alterations in these can alter the disease incidence. There is no universal agreement on diagnostic testing. There is no conclusive evidence from randomized trials that therapy alters pregnancy outcome in gestational diabetes. Therapy targeted at those fetuses shown to have evidence of hyperinsulinism may be the best way forward. Follow-up of women with early diagnosis, or who have required insulin during pregnancy is vital to allow prevention strategies against type 2 diabetes.

Clinical predictors for a high risk for the development of diabetes mellitus in the early puerperium in women with recent gestational diabetes mellitus

Objective: The purpose of this study was to identify which maternal, antepartum, or neonatal clinical parameters were predictive for a high risk of diabetes mellitus in the puerperium in women with recent gestational diabetes mellitus and to calculate the associated diabetes mellitus rates and odds ratios. Study design: One thousand six hundred thirty-six women underwent an oral glucose tolerance test within 1 to 4 months of delivery. Demographic, historic, and antenatal glycemic parameters and neonatal outcome parameters were tested by univariate and multivariate logistic regression for risk of postpartum diabetes mellitus. Continuous variables were divided into quartiles that compared the upper to lower quartile adjusted odds ratio and prevalence of diabetes mellitus. Results: Postpartum diabetes mellitus was diagnosed in 230 women (14.1%) according to the American Diabetes Association criteria (1997). No maternal demographic or neonatal parameters were significantly associated with diabetes mellitus. The final model of independent predictors in decreasing significance included the highest fasting plasma glucose level during pregnancy, any fasting plasma glucose level of ≥105 mg/dL (class A2), the area under the curve of pregnancy oral glucose tolerance test, gestational age at diagnosis, previous gestational diabetes mellitus history, and 50-g glucose challenge test results. The fasting plasma glucose level was the best discriminator, with a 21-fold (95% CI, 4.6-96.3) increased odds ratio comparing the 4th quartile (fasting plasma glucose level, >121 mg/dL; diabetes mellitus rate, 36.7%) to 1st quartile (fasting plasma glucose level, <95 mg/dL; diabetes mellitus rate, 0.5%). The presence of previous gestational diabetes mellitus or current class A2 gestational diabetes mellitus approximately doubled the odds ratio for diabetes mellitus. The odds ratio increased 3- to 4-fold when the area under the curve was ≥33.36 min · g/dL (4th quartile) or the glucose challenge test was ≥155 mg/dL (2nd–4th quartiles) and decreased >50% if gestational diabetes mellitus was diagnosed at >27 weeks (3rd-4th quartile). Conclusion: During pregnancy, the highest fasting glucose level, followed by the severity of glucose intolerance, and earlier gestational diabetes mellitus diagnosis were the best predictors for postpartum diabetes mellitus. Diabetic education should begin during pregnancy, especially for women who are identified to be at a high risk when they are highly motivated and under medical care. (Am J Obstet Gynecol 2002;186:751-6.)

Carbohydrate and diabetes: is the source or the amount of more importance?

There have been two approaches to examining the effects of carbohydrate on postprandial glycemia: 1) studies designed to determine the glycemic response of foods containing carbohydrate, regardless of the source, i.e., starch, sugar, or fiber (glycemic index [GI] of carbohydrates), and 2) studies comparing the glycemic response to equivalent amounts of starches or sugars. A number of food factors determine the glycemic response to carbohydrates: food form, digestibility, cooking, sugars, type of starch, presence of antinutrients, and second meal or lente effect. In people with diabetes, the severity of glucose intolerance and premeal glucose concentrations also influence the glycemic response. The GI attempts to classify individual foods (50-g portions) by the extent to which they raise blood glucose levels compared with a standard (reference carbohydrate), initially glucose and in later studies bread. Acute glycemic responses differ, however, when meals containing low GI foods are compared to meals containing high GI foods long term (measured by fructosamine or hemoglobin A1c), the outcomes are mixed. If there is an effect from the GI of foods on glycemia, it is modest at best. In other studies, when sucrose is substituted for a variety of starches--in meals or snacks and both acutely and for up to 6 weeks--the glycemic response is similar if the total amount of carbohydrate is similar. Therefore, the recommendation for persons with diabetes in regard to the glycemic effect of carbohydrates is that the total amount of carbohydrate in meals or snacks is more important than the source or type and is the first priority in the planning of meals or snacks. This has led to the implementation of carbohydrate counting, in which foods are listed as carbohydrate choices based on the amount and not the source of the carbohydrate.

Zottenreifungsstörungen der Plazenta beim Gestationsdiabetes - in Abhängigkeit von mütterlichen und fetalen Parametern des Glukosestoffwechsels

Glukosestoffwechselstörungen in der Schwangerschaft sind mit einem gehäuften Auftreten von Zottenreifungsstörungen der Plazenta assoziert. Die Frage ist, wie der orale Glukosetoleranztest (oGTT) und das Insulin im Fruchtwasser (FW-Ins) und im Nabelschnurblut (NS-Ins) mit der Inzidenz der Zottenunreife korrelieren. Insbesondere wurden die Auswirkungen einer grenzwertigen mütterlichen Glukosetoleranz (IGT) untersucht, für die bisher keine therapeutischen Maßnahmen gefordert wurden. Bei 248 Plazenten wurde morphologisch der Zottenreifestand untersucht und entsprechend des Schweregrades in schwere, mittelschwere und geringgradige Zottenreifungsstörung eingeteilt. Ein 75 g oGTT lag in allen Fällen vor (1 path. Wert = IGT, 2 path. Werte = GDM). FW-Ins-Proben wurde subpartal bei 141 Geburten gewonnen, NS-Ins-Proben wurden bei 224 Neugeborenen abgenommen. Es zeigte sich ein signifikanter Zusammenhang (p = 0,02) zwischen oGTT und Zottenunreife. Eine schwere Reifungsstörung fand sich bei normalem oGTT in 9%, bei IGT in 24% und bei GDM in 32%. Dazu kamen 14% bzw. 13% und 20% mittelschwere Reifungsstörungen. Das FW-lns zeigte ebenfalls eine signifikante Korrelation zur Zottenreife (p = 0,02), für das NS-lns ließ ein Trend feststellen (p = 0,09). Es besteht ein enger Zusammenhang zwischen dem Schweregrad einer mütterlichen Glukoseintoleranz und der Ausprägung von Zottenunreife. Bemerkenswert ist, daß sich beim IGT ein fast dreifach höherer Anteil von schwerer Zottenunreife ergab als bei normalem oGTT. Angesichts von insgesamt 37% Zottenreifungsstörung mit Funktionseinschränkung bei grenzwertiger Glukoseintoleranz (IGT) ist zu erwägen, Schwangere mit IGT sowohl bezüglich Stoffwechselkontrollen als auch fetaler Überwachung Gestationsdiabetikerinnen gleichzusetzen.

Clinical and laboratory characteristics in the families with diabetes and a mitochondrial tRNA LEU(UUR) gene mutation

We identified three families having a mutation in the mitochondrial tRNA LEU(UUR) gene at bp 3243 in 300 patients with non-insulin dependent diabetes mellitus (NIDDM), who had first degree relatives of patients with NIDDM. We found six individuals with diabetes, one with impaired glucose tolerance (IGT), and five with normal glucose tolerance (NGT) among three families. Insulin secretory response to oral glucose load was impaired in six diabetics, but was normal in IGT and NGT, and the proportion of mutant DNA in the blood did not always associate with the severity of glucose intolerance. Furthermore, both gender and obesity may influence the clinical expression of diabetes in three pairs with an age-matched brother-sister relationship with similar high mutation rate in blood samples. Thus, although patients with mitochondrial gene mutation had a high frequency of diabetes, the proportion of mutant DNA evaluated by blood samples may not necessarily indicate glucose intolerance in the members with the mutation. Unidentified factors including gender, aging, and obesity may alter the clinical manifestation of diabetes.

The relationship between large-for-gestational-age infants and glycemic control in women with gestational diabetes

In this prospective study 246 women with gestational diabetes were followed up to determine the characteristics of metabolic control associated with large-for-gestational-age infants. Memory-based reflectance meters were used for self-monitoring blood glucose. Ambulatory glucose profiles were produced to characterize glycemic control levels throughout pregnancy. With these novel approaches to the collection and representation of glucose data, the severity of glucose intolerance (hyperglycemia) was found to be associated with both maternal and neonatal morbidity in terms of infant size and cesarean section rate. By use of hierarchical cluster analysis to identify three groups on the basis of control levels (low <87 mg/dl, mid 87 to 105 mg/dl, high >105 mg/dl) we were able to show a positive outcome in the low group with reduced rates of large-for-gestational-age (2%) and macrosomatic (0%) infants. Furthermore, we showed that as mean blood glucose levels and instability in glycemic control increased from group to group, incidence of large-for-gestational-age and macrosomatic infants increased. Whereas obesity increased the relative risk of adverse neonatal outcome, type of treatment (insulin versus diet) did not appear to be significant. Appropriately monitored toward stability within a narrow range to achieve tight metabolic control, ambulatory glycemia in pregnancy is associated with a decreased risk of maternal and fetal complications.

Tropical pancreatic diabetes in South India: heterogeneity in clinical and biochemical profile.

Clinical and biochemical studies were carried out in 33 patients with diabetes secondary to chronic calcific, non-alcoholic pancreatitis (tropical pancreatic diabetes) and in 35 Type 2 (non-insulin-dependent) diabetic patients and 35 non-diabetic subjects. Despite lower body mass indices, only 25% of patients with tropical pancreatic diabetes had clinical evidence of malnutrition. There was no history of cassava ingestion. Mean serum cholesterol concentration was significantly lower in the tropical pancreatic diabetic patients (p less than 0.01) in comparison with the Type 2 diabetic patients or non-diabetic subjects, due to a significantly decreased concentration of LDL cholesterol (p less than 0.01) and VLDL cholesterol (p less than 0.05). Basal and post-glucose stimulated concentrations of serum C-peptide were highest in those pancreatic diabetic patients (n = 11) who responded to oral hypoglycaemic drugs, intermediate in the majority (n = 17), who were insulin dependent and ketosis resistant and negligible in a small sub-group (n = 5) who were ketosis prone. The occurrence of microangiopathy in pancreatic diabetic patients was common and similar to that in Type 2 diabetic patients. Thus, tropical pancreatic diabetes in South India appears to be heterogeneous with respect to level of nutrition, severity of glucose intolerance, B-cell function, response to therapy and the occurrence of microvascular complications.

Growth characteristics, glucose tolerance and insulin sensitivity of New Zealand obese mice

Comparisons were made between New Zealand obese (NZO) and control mice with respect to the following points: (1) the age of onset of obesity, (2) the frequency and severity of glucose intolerance, and (3) the degree of insulin sensivity. Total body composition analyses, intravenous glucose tolerance tests and insulin sensitivity tests were performed on the NZO and control strains. The results indicate that NZO mice have developed a significant chemical obesity by the fourth week of life while excessive body weight does not occur until after the twelfth week. Approximately two-thirds of the NZO mice demonstrate abnormal glucose tolerance tests although the degree of the glucose intolerance is relatively mild. The NZO mice are 4 to 5 times more resistant to insulin-induced convulsions than are the control mice.