Clinical characteristics, and time course of pancreatic beta-cell function and glutamic acid decarboxylase antibodies in Thai patients with adult-onset Type 1 diabetes: distinction between patients of rapid- and slow-onset.

In order to study the clinical characteristics, time course of beta cell function and glutamic acid decarboxylase antibodies (GAD65Ab) in Thai patients with adult-onset Type 1 diabetes and to examine the distinctive features between patients with rapid-and slow-onset, 61 Thai patients with Type 1 diabetes who had age of disease onset at or after 20 years were studied. All patients were treated with insulin at the time of study and had fasting C-peptide levels +/-0.33 nmol/l. Twenty-six (42.6%) were in rapid-onset and 35 (57.4%) were in slow-onset groups. Fourty-four of 61 (70.5%) were male. About three-fourths had body mass index (BMI) < 19 kg/m2 at the time of insulin therapy. Only 7 of 61 (11.5%) patients had ketoacidosis at first presentation. Five patients had associated autoimmune thyroid disease and 10 (16.7%) patients had family history of diabetes in first-degree relatives. GAD65Ab was positive in 31 patients (50.8%); 10 (38.5%) were in rapid-onset and 21 (60.0%) were in slow-onset groups. GAD65Ab particularly of high levels were persistently elevated during 3-4 years follow-up period. The persistence of GAD65Ab were not associated with changes in fasting C-peptide levels. At the time of insulin dependency, there were no distinctive clinical features between rapid- and slow-onset patients except higher fasting C-peptide (0.08+/-0.08 vs. 0.14+/-0.10 nmol/l; p = 0.023) and GAD65Ab levels (19.6+/-17.4 vs. 46.1+/-49.7 U/ml; p = 0.036) in slow-onset patients. Fasting C-peptide levels of patients in the latter group were also demonstrated to be higher after 3-4 years of follow-up. In conclusion, most Thai patients with adult-onset Type 1 diabetes in this study were male and had significant degree of weight loss and lean BMI prior to insulin therapy. The presence of GAD65Ab did not predict clinical features or rate of beta cell loss. Patients in rapid-onset group had lower fasting C-peptide and GAD65Ab levels than those of slow-onset group which confirms the slower process of beta cell failure in the latter.     

The effect of gender and age on growth hormone replacement in growth hormone-deficient patients.

We analyzed the effect of growth hormone replacement therapy (36 months) analyzed at a dose adjusted to maintain serum insulin-like growth factor-I level between the median and the upper end of the age-related reference range on bone mineral density, body composition, and carbohydrate metabolism with respect to gender and age in 20 adult patients (9 women, 11 men, mean age: 43 years, range: 21-61 years). The lumbar and femoral T-score was increased after 12 and after 18 months of therapy respectively in men (p < 0.001 and p = 0.002), but did not changed significantly in women. The increase of femoral T-score was greater in young men (< or = 45 years, n = 6) than old men (> 45 years, n = 5, p < 0.001). Body fat was lower in men than in women after 6 months (p = 0.002). The waist/hip ratio only decreased in women (p = 0.044). The waist circumference decreased in both genders after 6 months of therapy (p < 0.001), but more markedly in females than in males (p < 0.05). The sum of skinfold thicknesses was reduced in males after 6 months of therapy (p < 0.001). Changes in body composition parameters measured were independent of age. The glycosylated hemoglobin increased without sex or age difference after 12 months of initiation of therapy (p < 0.001), but fasting glucose and insulin levels did not change during the therapy. Our results indicate that the effect of growth hormone replacement on bone mineral content in adults is age- and gender-dependent, gender dependent on body composition, but independent of age and gender on carbohydrate metabolism.     

Metabolic profile and cardiovascular risk patterns of an Indian tribe living in the Amazon Region of Brazil

The Parkatêjê Indians, belonging to the Jê group and inhabiting the M?e Maria Reservation in the southeast of the state of Pará in the Amazon Region of Brazil, have suffered rapid and intensive cultural changes in recent years. This survey was designed to characterize the metabolic profile and the frequency of cardiovascular risk factors in this community. Ninety subjects (90.0% of the adult population without admixture) were investigated. Anthropometric measurements were performed and the following clinical characteristics measured: glycemia, serum insulin and proinsulin (fasting and 2-hr post 75 g of glucose load), beta-cell function (%B) and insulin sensitivity (%S) estimated by HOMA, HbA1c, GAD65 antibody, serum lipids, uric acid, creatinine, leptin, and blood pressure. Information about alcohol use, smoking, and medical history was obtained through individual interviews. The prevalences were: overweight, 67.8%; obesity, 14.4%; central obesity, 72.2%; hypertension, 4.4%; dyslipidemia, 44.4%; hyperuricemia, 5.6%; GAD65 antibody positivity, 4.4%; smoking, 25.6%; chronic alcohol use, 0.0%. One case of impaired glucose tolerance (1.1%) and one case of impaired fasting glycemia (1.1%) were diagnosed during this study and one case of diabetes (1.1%) was diagnosed previously. The diabetic woman was excluded from the analyses involving HbA1c, glycemia, insulin, proinsulin, %B, and %S. All creatinine values were normal. Blood pressure did not correlate with age, anthropometric measurements, insulin, proinsulin, and natural logarithm (ln) transformed %S. After adjustment for age and sex, there were positive correlations between total cholesterol and body mass index (BMI; r = 0.24), triglycerides and BMI (r = 0.44), triglycerides and waist-to-hip ratio (WHR; r = 0.52), In leptin and BMI (r = 0.41), In leptin and WHR (r = 0.29), uric acid and systolic blood pressure (r = 0.34), uric acid and triglycerides (r = 0.22). Systolic (r = 0.04; r = 0.70) and diastolic (r = 0.14; p = 0.18) blood pressure did not correlate with BMI. Ln leptin had a weak positive correlation with 2-hr insulin (r = 0.14) adjusted for age, sex, and BMI. The multiple linear regression model containing the variables sex, BMI, and 2-hr insulin concentrations explained 77.2% of the variation of ln leptin. In conclusion, the high rates of cardiovascular risk factors found among these Indians point to there being a high-risk group to develop diabetes and cardiovascular diseases. To reduce this risk they need to receive preventive interventions.     

Age associated differences in prevalence of individual rotterdam criteria and metabolic risk factors during reproductive age in 446 caucasian women with polycystic ovary syndrome

Clinical manifestations and metabolic risk factors may differ according to age in patients with polycystic ovary syndrome (PCOS). Therefore, a retrospective trans-sectional study in academic tertiary-care medical center was designed. A cohort of 446 premenopausal, Caucasian women (age range 15-49 years) with PCOS were divided into 4 subgroups according to age: group 1 (15-19 years, n=42), group 2 (20-29 years, n=180), group 3 (30-39 years, n=187), group 4 (40-49 years, n=37) and underwent clinical evaluation (Ferriman-Gallwey score, BMI, waist, blood pressure), hormone analyses (sex hormones, fasting lipids, insulin, glucose), transvaginal ultrasound, oral glucose tolerance tests (OGTT) (n=234), and ACTH tests (n=201). BMI, waist, Ferriman-Gallwey score, blood pressure, and lipid profile were higher in older vs. younger age groups whereas androgen levels were lower. Measures of insulin resistance were unchanged between age groups, but glucose levels were significantly higher in older age groups. Rotterdam criteria: The prevalence of PCO and biochemical hyperandrogenism decreased in the oldest age group whereas clinical hyperandrogenism increased. Young patients are characterized by PCO and biochemical hyperandrogenism, whereas older patients are more obese with more severe hirsutism and more cardiovascular and metabolic risk factors.     

Efficacy of liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, on body weight, eating behavior, and glycemic control, in Japanese obese type 2 diabetes

ABSTRACT: BACKGROUND: We recently reported that short-term treatment with liraglutide (20.0 +/- 6.4 days) reduced body weight and improved some scales of eating behavior in Japanese type 2 diabetes inpatients. However, it remained uncertain whether such liraglutide-induced improvement is maintained after discharge from the hospital. The aim of the present study was to determine the long-term effects of liraglutide on body weight, glycemic control, and eating behavior in Japanese obese type 2 diabetics. METHODS: Patients with obesity (body mass index (BMI) >25 kg/m2) and type 2 diabetes were hospitalized at Osaka University Hospital between November 2010 and December 2011. BMI and glycated hemoglobin (HbA1c) were examined on admission, at discharge and at 1, 3, and 6 months after discharge. For the liraglutide group (BMI; 31.3 +/- 5.3 kg/m2, n = 29), patients were introduced to liraglutide after correction of hyperglycemic by insulin or oral glucose-lowering drugs and maintained on liraglutide after discharge. Eating behavior was assessed in patients treated with liraglutide using The Guideline For Obesity questionnaire issued by the Japan Society for the Study of Obesity, at admission, discharge, 3 and 6 months after discharge. For the insulin group (BMI; 29.1 +/- 3.0 kg/m2, n = 28), each patient was treated with insulin during hospitalization and glycemic control maintained by insulin after discharge. RESULTS: Liraglutide induced significant and persistent weight loss from admission up to 6 months after discharge, while no change in body weight after discharge was noted in the insulin group. Liraglutide produced significant improvements in all major scores of eating behavior questionnaire items and such effect was maintained at 6 months after discharge. Weight loss correlated significantly with the decrease in scores for recognition of weight and constitution, sense of hunger, and eating style. CONCLUSION: Liraglutide produced meaningful long-term weight loss and significantly improved eating behavior in obese Japanese patients with type 2 diabetes.     

Blood serum concentration of lipids and lipoproteins and body composition

The purpose of this study is the analysis of the relationship of blood serum apolipoprotein E (apoE), total cholesterol (TC), triglycerides (TG) and high-density and low-density lipoproteins (HDL, LDL), with body mass index (BMI), relative body surface area (RBSA) and body muscle (BM) and body fat (BF). The subjects are males and females aged 14-16 (adolescent age group 1: n1M = 141, n1F = 151) and 18-25 (young adult group 2, n2M = 16, n2F = 46). Significant correlations of serum TG and HDL with somatometric indicators were not observed. In the female samples, TC content directly correlates (p < 0.05) with BF (r1 = 0.164; r2 = 0.418) and negatively correlates with BM (r1 = -0.165; r2 = -0.352). The blood serum concentration of apoE is significantly correlated with body composition in adolescent females (for BF r1 = -0.168; for BM r1 = 0.266; p < 0.05); in males 14-16 years old, the both correlations have a significance level p < 0.06. In young adult females TC and LDL content negatively correlates with RBSA (r2 = -0.386 and -0.377 respectively; p < 0.05) and positively correlates with BMI (r2 = 0.413 and 0.415 respectively; p < 0.05). Adolescent females and young adult females have opposite relationships between FC and apoE concentration. In females 14-15 years old apoE concentration decreases as FC increases. In females 16-17 the correlation disappears, and in older females apoE concentration and FC increase together.     

Childhood Overweight Status Predicts Diabetes at Age 21 Years: A Follow‐up Study

We examined the prospective association of childhood BMI z‐score and BMI categories (normal or overweight) with young adult diabetes, controlling for early life, childhood, and adolescence factors. A subsample of 2,639 young adults from the Mater–University study of pregnancy (MUSP) and its outcomes, a prospective birth cohort who were born in Brisbane, Australia and for whom we had measured height and weight at 5 years and self‐reported diabetes at age 21 years. The risk of developing diabetes by age 21 years was greater among young adults who had greater BMI z‐score or were overweight at age 5 years than those who had normal BMI at age 5 years. Young adults who were overweight at age 5 years had an increased odds ratio of 2.60 (95% confidence interval (CI): 1.29, 5.22, in age‐ and sex‐adjusted model) of experiencing diabetes by age 21 years. Adjustment for potential confounders and mediators including intrauterine environmental factors, childhood dietary patterns, television watching, participation in sports and exercise, and current weight, did not substantively alter these associations. Overweight and increasing BMI z‐score at childhood is an independent predictor of young adult's type 1 and type 2 diabetes. Findings of this study suggest that childhood BMI may be central to the development and rising incidence of all diabetes.     

Economic Impact of the Clinical Benefits of Bariatric Surgery in Diabetes Patients With BMI ≥35 kg/m2

The medical costs for a type 2 diabetes patient are two to four times greater than the costs for a patient without diabetes. Bariatric surgery is the most effective weight‐loss therapy and has marked therapeutic effects on diabetes. We estimate the economic effect of the clinical benefits of bariatric surgery for diabetes patients with BMI ≥35 kg/m². Using an administrative claims database of privately insured patients covering 8.5 million lives 1999–2007, we identify obese patients with diabetes, aged 18–65 years, who were treated with bariatric surgery identified using Healthcare Common Procedure Coding System codes. These patients were matched with nonsurgery control patients on demographic factors, comorbidities, and health‐care costs. The overall return on investment (RoI) associated with bariatric surgery was calculated using multivariate analysis. Surgery and control patients were compared postindex with respect to diagnostic claims for diabetes, diabetes medication claims, and adjusted diabetes medication and supply costs. Surgery costs were fully recovered after 26 months for laparoscopic surgery. At month 6, 28% of surgery patients had a diabetes diagnosis, compared to 74% of control patients (P < 0.001). Among preindex insulin users, insulin use dropped to 43% by month 3 for surgery patients, vs. 84% for controls (P < 0.001). By month 1, medication and supply costs were significantly lower for surgery patients (P < 0.001). The therapeutic benefits of bariatric surgery on diabetes translate into considerable economic benefits. These data suggest that surgical therapy is clinically more effective and ultimately less expensive than standard therapy for diabetes patients with BMI ≥35 kg/m².     

安立泽联合胰岛素治疗单独胰岛素降糖欠佳的高龄 2 型糖尿病患者临床观察

目的：观察安立泽应用于单独胰岛素治疗血糖控制欠佳的高龄2 型糖尿病患者的疗效及安全性。方法：200 例高龄2型糖尿 病胰岛素降糖欠佳的患者（空腹血糖控制在7.8-13.9mmol/L范围内）,随机分成对照组和治疗组,对照组采用胰岛素加安慰剂治 疗80 例;治疗组120 例,分为A、B、C三组,每组40 例,A、B、C三组分别在继续应用胰岛素治疗的基础上加服安立泽4mg/d、 5mg/d、6mg/d,疗程三个月。观测治疗组和对照组治疗前后FPG 及PPG、HbA1C、BMI 和胰岛素用量的改变及治疗的安全性。结 果：对照组和治疗组治疗前的各指标无明显差异（P＞0.05）;A、B、C三组在治疗后1 个月和3 个月FPG、PPG、HbA1C均有明显的 下降（P＜0.05,P＜0.01）,而对照组治疗前后FIG、PPG、HbA1C 略有下降,差异不明显（P＞0.05）;A、B、C 三组胰岛素的用量及体 重指数较治疗前均略有下降,三组间无显著性差异;对照组和治疗组的不良反应发生率无显著差异。结论：对高龄2 型糖尿病单 用胰岛素治疗血糖控制欠佳的患者,加用安立泽治疗,可使糖尿病相关指标得以良好的控制,减少糖尿病患者每日胰岛素用量, 临床毒副作用较小。     

Elevated serum GGT concentrations predict reduced insulin sensitivity and increased intrahepatic lipids.

Elevated serum gamma-glutamyltransferase (GGT) concentrations have been related to features of the metabolic syndrome as well as increased risk of cardiovascular and liver disease. More recently, elevated GGT levels were shown to predict development of type 2 diabetes in a longitudinal study from Korea. The aim of the present study was to test the hypothesis that serum GGT is associated with glucose tolerance, insulin sensitivity and beta-cell function in a healthy, non-diabetic Caucasian population from the Tübingen family study. Insulin sensitivity was estimated by oGTT (n = 850) or measured by hyperinsulinemic euglycemic clamp (n = 245), respectively. A subgroup (n = 70) underwent additional determination of intrahepatic lipid content using 1H magnetic resonance spectroscopy. Serum GGT was positively correlated with two-hour glucose during oGTT (r = 0.15, p < 0.0001) and negatively correlated with insulin sensitivity from oGTT (r = -0.31, p < 0.0001) and clamp (r = -0.27, p < 0.0001). The relationship between GGT and insulin sensitivity remained significant after adjusting for sex, age, BMI, and AST using multivariate regression analysis. Inclusion of serum triglyceride levels as a parameter of lipid metabolism kept the relationship significant in the oGTT group (p < 0.0001), but not in the smaller clamp group (p = 0.11). Additionally, serum GGT was positively correlated with hepatic lipid content (r = 0.49, p < 0.001) independent of sex, age, BMI, AST or serum triglycerides. There was no significant correlation between GGT and the index for beta-cell function after adjusting for age, sex, BMI and insulin sensitivity (p = 0.74). In conclusion, elevated serum GGT levels predict glucose intolerance probably via insulin resistance rather than beta-cell dysfunction. This may be primarily related to hepatic insulin resistance and increased intrahepatic lipids. The association observed between elevated hepatic lipids and reduced insulin sensitivity might explain the increased diabetes risk observed in subjects with elevated serum GGT concentrations. In the absence of overt liver disease, elevated serum GGT concentrations may point the clinician to incipient disturbances in the glucose metabolism.     

The interaction of childhood height and childhood BMI in the prediction of young adult BMI

The purpose of this study was to examine the interaction of childhood height and childhood BMI in the prediction of young adult BMI. The 2,802 subjects in this study were from the Child and Adolescent Trial for Cardiovascular Health (CATCH). The subjects' heights and weights were measured in 3rd grade (mean age 8.7 years) and again in 12th grade (mean age 18.3 years). The associations and interactions between height (cm) and BMI (kg/m(2)) were assessed using mixed linear regression models with adult BMI as the dependent variable. We found a significant interaction between childhood height and childhood BMI in the prediction of adult BMI (P < 0.0001). Stratification by Centers for Disease Control and Prevention (CDC) reference quintiles revealed that a positive association between childhood height and adult BMI existed only for those subjects in the top quintile of childhood BMI, within whom predicted adult BMI ranged from 27.5 (95% confidence interval = 26.4-28.6) for those in the shortest height quintile to 30.2 (95% confidence interval = 29.7-30.6) for those in the highest height quintile. Among children with high BMI levels, those who were taller, as compared to those who were shorter, had significantly higher young adult BMI levels. This pattern seems primarily due to the positive association of childhood height and childhood BMI. Clinicians should recognize the risk of excess body weight in young adulthood for all children who have a high BMI, and pay special attention to those who are tall, because their childhood height will not protect them from subsequent weight gain and elevated BMI.     

Earlier Menarche Is Associated with Lower Insulin Sensitivity and Increased Adiposity in Young Adult Women

Objective

We aimed to assess whether age at menarche was associated with insulin sensitivity in young adult women.

Methods

We studied 54 healthy young women aged 20–30 years. Participants were grouped according to age at menarche: Early (≤11.0 years; n=13), Average (>12.0 and ≤13.0 years; n=28), and Late (≥14.0 years, n=13). Primary outcome was insulin sensitivity measured using intravenous glucose tolerance tests and Bergman’s minimal model. Body composition was assessed using whole-body dual-energy X-ray absorptiometry.

Results

Earlier menarche was associated with lower insulin sensitivity (p=0.015). There was also a continuous increase in adiposity with younger age at menarche, which was associated with increased weight (p=0.001), BMI (p=0.002), total body fat (p=0.049), and truncal fat (p=0.020). Stratified analyses showed that insulin sensitivity in Early women (5.5 x10^-4·min^-1(mU/l)) was lower than in Average (8.0 x10^-4·min^-1(mU/l), p=0.021) and Late (8.6 x10^-4·min^-1(mU/l), p=0.033) groups. Early women (weight=66.1 kg; BMI=24.1 kg/m²) were considerably heavier and fatter than Average (59.0 kg, p=0.004; 21.4 kg/m², p=0.002) and Late (57.0 kg, p=0.001; 20.8 kg/m², p=0.0009) women.

Conclusions

Early menarche is associated with lower insulin sensitivity and increased adiposity in young adulthood, potentially increasing the risk of type 2 diabetes and the metabolic syndrome later in life.     

Patient Behaviors Associated with Optimum Glycemic Outcomes with Sensor-Augmented Pump Therapy: Insights from The Star 3 Study

ObjectiveThe purpose of this analysis was to identify patient behaviors that led to optimum glycemic outcomes in subjects with type 1 diabetes (T1DM) who transitioned from multiple daily injections (MDI) therapy to sensor-augmented pump (SAP) therapy.MethodsSensor-augmented pump Therapy for A1C Reduction (STAR 3), a randomized controlled trial, assigned 485 suboptimally controlled T1DM subjects to either MDI therapy (n = 241) or SAP therapy (n = 244). We categorized subjects in the latter group according to age at enrollment and glycated hemoglobin (A1C) value after using the SAP system for 12 months. Pairwise comparisons of how the pump features were used between SAP subjects with the highest and lowest end-of-study A1C values were made via t tests.ResultsLarger decreases in A1C values were significantly correlated with increasing sensor use in both the adult and pediatric age groups. Subjects in the low-A1C cohorts of both pediatric and adult age groups gave themselves smaller and more frequent boluses and used the Bolus Wizard bolus estimation calculator more frequently than subjects in age-matched high-A1C cohorts. Children in the low-A1C cohort used less insulin than children in the high-A1C cohort. There was no additional hypoglyce-mia in either the adult or pediatric low-A1C cohorts versus their high-A1C counterparts.ConclusionsBoth adult and pediatric patients with T1DM on SAP who use CGM sensors more often will have a greater decrease in their A1C values than those who do not demonstrate these behaviors. Routine use of CGM may lead to smaller and more frequent bolus dosing, enabling this population to safely reach their A1C goals. (Endocr Pract. 2015;21:41-45)     

Height at Late Adolescence and Incident Diabetes among Young Men

Background

Short stature was suggested as a risk factor for diabetes onset among middle age individuals, but whether this is the case among young adults is unclear. Our goal was to assess the association between height and incident diabetes among young men.

Methods and Findings

Incident diabetes was assessed among 32,055 men with no history of diabetes, from the prospectively followed young adults of the MELANY cohort. Height was measured at two time points; at adolescence (mean age 17.4±0.3 years) and grouped according to the US-CDC percentiles and at young adulthood (mean age 31.0±5.6 years). Cox proportional hazards models were applied. There were 702 new cases of diabetes during a mean follow-up of 6.3±4.3 years. There was a significant increase in the crude diabetes incidence rate with decreasing adolescent height percentile, from 4.23 cases/10⁴ person-years in the <10^th percentile group to 2.44 cases/10⁴ person-years in the 75^th≤ percentile group. These results persisted when clinical and biochemical diabetes risk factors were included in multivariable models. Compared to the 75^th≤ percentile group, height below the 10^th percentile was associated with a hazard ratio (HR) of 1.64 (95%CI 1.09–2.46, p = 0.017) for incident diabetes after adjustment for age, body mass index (BMI), fasting plasma glucose, HDL-cholesterol and triglyceride levels, white blood cells count, socioeconomic status, country of origin, family history of diabetes, sleep quality and physical activity. At age 30 years, each 1-cm decrement in adult height was associated with a 2.5% increase in diabetes adjusted risk (HR 1.025, 95%CI 1.01–1.04, p = 0.001).

Conclusions

Shorter height at late adolescence or young adulthood was associated with an increased risk of incident diabetes among young men, independent of BMI and other diabetes risk factors.     

Fetal growth and the physiological control of glucose tolerance in adults: a minimal model analysis

Although there is now substantial evidence linking low birthweight with impaired glucose tolerance and type 2 diabetes in adult life, the extent to which reduced fetal growth is associated with impaired insulin sensitivity, defective insulin secretion, or a combination of both factors is not clear. We have therefore examined the relationships between birth size and both insulin sensitivity and insulin secretion as assessed by an intravenous glucose tolerance test with minimal model analysis in 163 men and women, aged 20 yr, born at term in Adelaide, South Australia. Birth size did not correlate with body mass index or fat distribution in men or women. Men who were lighter or shorter as babies were less insulin sensitive (P = 0.03 and P = 0.01, respectively), independently of their body mass index or body fat distribution. They also had higher insulin secretion (P = 0.007 and P = 0.006) and increased glucose effectiveness (P = 0.003 and P = 0.003). Overall glucose tolerance, however, did not correlate with birth size, suggesting that the reduced insulin sensitivity was being compensated for by an increase in insulin secretion and insulin-independent glucose disposal. There were no relationships between birth size and insulin sensitivity or insulin secretion in women. These results show that small size at birth is associated with increased insulin resistance and hyperinsulinemia in young adult life but that these relationships are restricted to the male gender in this age group.     

Effects of a combination of recombinant human growth hormone with metformin on glucose metabolism and body composition in patients with metabolic syndrome.

Abdominal obesity and insulin resistance are central findings in metabolic syndrome. Since treatment with recombinant human growth hormone (rhGH) can reduce body fat mass in patients with organic GH deficiency, rhGH therapy may also have favourable effects on patients with metabolic syndrome. However, due to the highly increased risk for type 2 diabetes in these patients, strategies are needed to reduce the antagonistic effect of rhGH against insulin. We conducted a 18-month randomised, double-blind, placebo-controlled study to assess the effect of rhGH in combination with metformin (Met) in patients with metabolic syndrome. 25 obese men (55 +/- 6 years, BMI 33.4 +/- 2.9 kg/m (2)) with mildly elevated fasting plasma glucose (FPG) levels at screening (6.1-8.0 mmol/l) were included. All patients received metformin (850 mg twice daily) either alone or in combination with rhGH (daily dose 9.5 microg/kg body weight). An oGTT was performed at baseline, after 6 weeks, and after 3, 6, 12, and 18 months of therapy. Glucose disposal rate (GDR) was measured by euglycemic hyperinsulinemic clamp at 0 and 18 months and body composition was measured by DEXA every 6 months. In the Met + GH group, IGF-I increased from 146 +/- 56 microg/l to 373 +/- 111 microg/l (mean +/- SD) after 3 months and remained stable after that. BMI did not change significantly in either group during the study. Total body fat decreased by -4.3 +/- 5.4 kg in the Met + GH group and by -2.7 +/- 2.9 kg in the Met + Placebo group (differences between the two groups: p = n. s.). Waist circumference decreased in both groups (Met + GH: 118 +/- 8 cm at baseline, 112 +/- 10 cm after 18 months; Met + Placebo: 114 +/- 7 cm vs. 109 +/- 8 cm; differences between the two groups: p = 0.096). In the Met + GH group, FPG increased significantly after 6 months (5.9 +/- 0.7 vs. 6.7 +/- 0.4 mmol/l; p = 0.005), but subsequently decreased to baseline levels (18 months: 5.8 +/- 0.2 mmol/l). FPG remained stable in the Met + Placebo group until 12 months had elapsed, and then slightly decreased (baseline: 6.2 +/- 0.3, 18 months: 5.5 +/- 0.6 mmol/l, p = 0.02). No significant changes were seen in either group regarding glucose and insulin AUC during oGTT or HbA (1c) levels. GDR at 18 months increased by 20 +/- 39% in Met + GH-group and decreased by -11 +/- 25% in the Met + Placebo group (differences between the two groups: p = 0.07). In conclusion, treatment of patients with metabolic syndrome and elevated FPG levels did not cause sustained negative effects on glucose metabolism or insulin sensitivity if given in combination with metformin. However, since our data did not show significant differences between the two treatment groups with respect to body composition or lipid metabolism, future studies including larger numbers of patients will have to clarify whether the positive effects of rhGH on cardiovascular risk factors that have been shown in patients with GH deficiency are also present in patients with metabolic syndrome, and are additive to the effects of metformin.     

The Clinical And Metabolic Characteristics Of Young-Onset Ketosis-Prone Type 2 Diabetes In China

Objective: To investigate the prevalence and clinical characteristics of ketosis-prone type 2 diabetes (KPD) in Chinese patients with young-onset diabetes.Methods: A total of 238 young diabetic patients were recruited from our inpatient department from January 1, 2012, to December 28, 2014. KPD was defined as diabetes without precipitating illness and with the presence of ketosis or diabetic ketoacidosis in the absence of autoantibodies at the time of diagnosis. We reviewed the clinical characteristics and disease progression of this group of patients.Results: Eighteen patients fulfilled the criteria for KPD, and the prevalence of patients with KPD was 7.6%. The mean (SD) age of the KPD group at the time of diagnosis of diabetes was 27.6 (4.85) years, and these patients were predominantly male (male to female ratio, 8:1) and had a high proportion of obesity and new-onset diabetes and a strong family history of diabetes. β-Cell function in the KPD group was intermediate between type 1 and type 2 diabetes. Patients with KPD had the highest levels of glycated hemoglobin, triglycerides, total cholesterol, and free fatty acids and the lowest levels of high-density lipoprotein. After 3 to 12 months of follow-up, 17 of 18 patients with KPD (94.4%) were able to discontinue insulin therapy, and 11 patients (61.1%) were managed with diet or exercise alone.Conclusion: KPD patients accounted for 7.6% of the diabetic patients requiring admission to a large urban hospital in China, with an age of onset of diabetes of ≤35 years. These patients are more likely to be male, have abnormal lipid metabolism, and have more reversible β-cell dysfunction.Abbreviations:BMI = body mass indexDKA = diabetic ketoacidosisGAD 65 = glutamate decarboxylase 65HbA _1c = glycated hemoglobinICAs = islet-cell antibodiesKPD = ketosis-prone type 2 diabetes mellitusLADA = latent autoimmune diabetes in an adultMIDD = maternally inherited diabetes and deafnessMODY = maturityonset diabetes of the youngT1DM = type 1 diabetes mellitusT2DM = type 2 diabetes mellitus     

Insulin adjustment by a diabetes nurse educator improves glucose control in insulin-requiring diabetic patients: a randomized trial

BACKGROUND: Diabetic patients taking insulin often have suboptimal glucose control, and standard methods of health care delivery are ineffective in improving such control. This study was undertaken to determine if insulin adjustment according to advice provided by telephone by a diabetes nurse educator could lead to better glucose control, as indicated by level of glycated hemoglobin (HbA1c). METHODS: The authors conducted a prospective randomized trial involving 46 insulin-requiring diabetic patients who had poor glucose control (HbA1c of 0.085 or more). Eligible patients were those already taking insulin and receiving endocrinologist-directed care through a diabetes centre and whose most recent HbA1c level was 0.085 or higher. The patients were randomly assigned to receive standard care or to have regular telephone contact with a diabetes nurse educator for advice about adjustment of insulin therapy. RESULTS: At baseline there was no statistically significant difference between the 2 groups in terms of HbA1c level (mean [and standard deviation] for standard-care group 0.094 [0.008] and for intervention group 0.096 [0.010]), age, sex, type or duration of diabetes, duration of insulin therapy or complications. After 6 months, the mean HbA1c level in the standard-care group was 0.089 (0.010), which was not significantly different from the mean level at baseline. However, the mean HbA1c level in the intervention group had fallen to 0.078 (0.008), which was significantly lower than both the level at baseline for that group (p < 0.001) and the level for the standard-care group at 6 months (p < 0.01). INTERPRETATION: Insulin adjustment according to advice from a diabetes nurse educator is an effective method of improving glucose control in insulin-requiring diabetic patients.     

血清成纤维细胞生长因子2、21、23与妊娠期糖尿病患者新生儿结局的关系

摘要 目的：探讨血清成纤维细胞生长因子2（FGF2）、成纤维细胞生长因子21（FGF21）、成纤维细胞生长因子23（FGF23）与妊娠期糖尿病（GDM）患者新生儿结局的关系。方法：选取2021年1月～2022年12月期间于我院产检的妊娠24～28周孕妇147例,均进行口服葡萄糖耐量试验（OGTT）,根据OGTT结果分为GDM组（n=86）和非GDM组（n=61）。其中GDM组根据新生儿结局分为不良组（n=21）和良好组（n=65）。对比非GDM组、GDM组的血清FGF2、FGF21、FGF23水平及新生儿结局情况。对比不良组和良好组的血清FGF2、FGF21、FGF23水平。单因素及多因素Logistic回归分析影响GDM患者新生儿结局的影响因素。结果：GDM组的血清FGF2、FGF21、FGF23水平均高于非GDM组（P<0.05）。GDM组的不良新生儿结局总发生率高于非GDM组（P<0.05）。不良组的血清FGF2、FGF21、FGF23水平均高于良好组（P<0.05）。单因素分析显示,GDM患者不良新生儿结局与年龄、孕前体质量指数（BMI）、分娩前BMI、空腹血糖（FPG）、餐后2 h血糖（2hPG）、空腹胰岛素（FINS）、胰岛素抵抗指数（HOMA-IR）有关（P<0.05）。多因素分析结果显示,年龄偏高、FPG偏高、孕前BMI偏高、2hPG偏高、分娩前BMI偏高、HOMA-IR偏高、FGF2偏高、FINS偏高、FGF21偏高、FGF23偏高均是GDM患者不良新生儿结局的危险因素（P<0.05）。结论：GDM患者血清FGF2、FGF21、FGF23水平升高,其与年龄、孕前BMI、分娩前BMI、FPG、2hPG、FINS、HOMA-IR偏高均是导致GDM患者不良新生儿结局的危险因素。     

Factors Associated With Insulin Pump Discontinuation in Adults With Diabetes: A Time-to-Invent Analysis and Prediction Model

ObjectiveInsulin pump discontinuation has mostly been studied in children and adolescents living with diabetes. We aimed to assess the rate of insulin pump continuation in a population of adult patients with diabetes, at 18 months after initiation; determine the factors associated with pump discontinuation; and develop a simple prediction model.MethodsThis single-center, retrospective study included all adult patients with type 1 diabetes or type 2 diabetes who started insulin pump treatment between January 2015 and June 2018. The exclusion criteria were pregnancy, short-term pregnancy plans, and insulin pump discontinuation within the previous 6 months. The probability of insulin pump continuation after 18 months was estimated using the Kaplan-Meier method. Factors associated with insulin pump discontinuation were studied using a Cox regression model, and an exponential model was built for prediction purposes.ResultsThe study included 315 patients. The mean age was 41 years, the mean duration of diabetes was 16 years, 50% were men, 74% had type 1 diabetes, and the mean hemoglobin A1c level was 9.1% (76 mmol/mol). After 18 months, the rate of insulin pump continuation was 0.80 (95% Confidence Interval (CI), 0.76-0.85). By multivariate analysis, the occurrence of severe hypoglycemia in the previous year was associated with insulin pump discontinuation (hazard ratio, 2.42; 95% CI, 1.30-4.51), while other factors did not reach statistical significance.ConclusionInsulin pump discontinuation occurred in 20% of patients at 18 months after initiation and was mainly associated with a recent history of severe hypoglycemia. The type of diabetes and glycemic control at baseline were not associated with treatment discontinuation.