Diabetes in Cystic Fibrosis: Multicenter Screening Results Based on Current Guidelines

Background

Published estimates on age-dependent frequency of diabetes in cystic fibrosis (CF) vary widely, and are based mostly on older data. However, CF treatment and prevention of comorbidities changed over recent years. In many studies, definition of cystic fibrosis-related diabetes (CFRD) is not in line with current guideline recommendations. Therefore, we evaluated age-dependent occurrence of glucose abnormalities and associated risk factors in CF patients who participated in a multicenter screening program using oral glucose tolerance tests (OGTT).

Methods

Between 2001 and 2010, 43 specialized CF centers from Germany and Austria serially performed 5,179 standardized OGTTs in 1,658 clinically stable, non-pregnant CF patients with no prior steroid medication or lung transplantation. Age-dependent occurrence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG+IGT, one (DGT) or two consecutive (CFRD) diabetic OGTTs was analyzed, using Kaplan Meier curves. Cox proportional-hazards models were created to elucidate the influence of sex or underweight.

Results

At baseline/last OGTT, median age was 15.9 years/18.2 years and 30.6%/31.8% of patients were underweight. 25% of patients showed IFG at age 14.3 years; IGT at age 16.3 years; IFG+IGT combined at age 17.7 years. DGT was observed in 25% of patients at age 22.6 years; CFRD at age 34.5 years. Females had a 3.54 [95% CI 1.23–10.18] times higher risk for CFRD; risk for DGT was 2.21 [1.22–3.98] times higher. Underweight was a risk factor for IGT (HR [95% CI]: 1.38 [1.11–1.71]) and IFG+IGT (1.43 [1.11–1.83]), and in males also for DGT (1.49 [1.09–2.04]).

Conclusions/Significance

If confirmation of diabetes by a second test is required, as recommended in current guidelines, age at CFRD diagnosis was higher compared to most previous studies. However, known risk factors for glucose abnormalities in CF were confirmed. Confirmation of diabetic OGT by a repeat test is important for a consistent diagnosis of CFRD.     

Predicting insulin resistance using the triglyceride-to-high-density lipoprotein cholesterol ratio in Taiwanese adults

Background

Heart type fatty acid binding protein (H-FABP) has been closely associated with acute coronary syndrome, cardiac abnormalities, stroke, and obstructive sleep disorder in previous studies. The aim of this study was to evaluate and compare the serum H-FABP levels and carotid artery intima-media thickness (CIMT) between patients with prediabetes and control subjects.

Research design and methods

We measured serum H-FABP levels in 58 prediabetic patients, 29 with impaired fasting glucose (IFG) and 29 with impaired glucose tolerance (IGT) and 28 age-, sex- and body mass index-matched control subjects using a sandwich enzyme-linked immunosorbent assay (ELISA), and in order to measure CIMT, all participants underwent high-resolution B-mode ultrasonography.

Results

Serum H-FABP levels were significantly elevated in pre-diabetic patients when compared with that of control subjects (IFG: 32.5 ± 34.2 ng/dL, IGT: 45.4 ± 45.8 ng/dL, control: 16.8 ± 14.9 ng/dL; p = 0.011). The difference in means of H-FABP levels between patients with IGT or IFG and control subjects was significant (p = 0.010 and p = 0.009, respectively). CIMT was higher in the pre-diabetic groups compared with the control group (IFG: 0.6 ± 0.1, IGT: 0.6 ± 0.1, control: 0.5 ± 0.1; p < 0.001), and H-FABP level was positively correlated with CIMT (p < 0.001, rho = 0.626).

Conclusion

Our results indicate that patients with pre-diabetes are at increased risk for cardiovascular disease. In addition, serum H-FABP levels could represent a useful marker for myocardial performance in patients with IFG and IGT.     

Metformin modifies the exercise training effects on risk factors for cardiovascular disease in impaired glucose tolerant adults

Impaired glucose tolerant (IGT) adults are at elevated risk for cardiovascular disease (CVD). Exercise or metformin reduce CVD risk, but the efficacy of combining treatments is unclear.

Objective:

To determine the effects of exercise training plus metformin (EM), compared with each treatment alone, on CVD risk factors in IGT adults.

Design and Methods:

Subjects were assigned to placebo (P), metformin (M), exercise training plus placebo (EP), or EM (8/group). In a double‐blind design, P or 2,000 mg/d of M were administered for 12 weeks and half performed aerobic and resistance training 3 days/week for ～60 min/day at 70% pretraining heart rate peak. Outcomes included adiposity, blood pressure (BP), lipids, and high sensitivity C‐reactive protein (hs‐CRP). Z‐scores were calculated to determine metabolic syndrome severity.

Results:

M and EM, but not EP, decreased body weight compared with P (P < 0.05). M and EP lowered systolic blood pressure by 6% (P < 0.05), diastolic blood pressure by 6% (P < 0.05), and hs‐CRP by 20% (M: trend P = 0.06; EP: P < 0.05) compared with P. Treatments raised high‐density lipoprotein cholesterol (P < 0.05; EM: trend P = 0.06) compared with P and lowered triacyglycerol (P < 0.05) and metabolic syndrome Z‐score compared with baseline (EP; trend P = 0.07 and EM or M; P < 0.05).

Conclusions:

Although exercise and/or metformin improve some CVD risk factors, only training or metformin alone lowered hs‐CRP and BP. Thus, metformin may attenuate the effects of training on some CVD risk factors and metabolic syndrome severity in IGT adults.     

Prediabetes Phenotype Influences Improvements in Glucose Homeostasis with Resistance Training

Purpose

To determine if prediabetes phenotype influences improvements in glucose homeostasis with resistance training (RT).

Methods

Older, overweight individuals with prediabetes (n = 159; aged 60±5 yrs; BMI 33±4 kg/m²) completed a supervised RT program twice per week for 12 weeks. Body weight and composition, strength, fasting plasma glucose, 2-hr oral glucose tolerance, and Matsuda-Defronza estimated insulin sensitivity index (ISI) were assessed before and after the intervention. Participants were categorized according to their baseline prediabetes phenotype as impaired fasting glucose only (IFG) (n = 73), impaired glucose tolerance only (IGT) (n = 21), or combined IFG and IGT (IFG/IGT) (n = 65).

Results

Chest press and leg press strength increased 27% and 18%, respectively, following the 12-week RT program (both p<0.05). Waist circumference (-1.0%; pre 109.3±10.3 cm, post 108.2±10.6 cm) and body fat (-0.6%; pre 43.7±6.8%, post 43.1±6.8%) declined, and lean body mass (+1.3%; pre 52.0±10.4 kg, post 52.7±10.7 kg) increased following the intervention. Fasting glucose concentrations did not change (p>0.05) following the intervention. However, 2-hr oral glucose tolerance improved in those with IGT (pre 8.94±0.72 mmol/l, post 7.83±1.11 mmol/l, p<0.05) and IFG/IGT (pre 9.66±1.11mmol/l, post 8.60±2.00 mmol/l) but not in those with IFG (pre 6.27±1.28mmol/l, post 6.33± 1.55 mmol/l). There were no significant changes in ISI or glucose area under the curve following the RT program.

Conclusions

RT without dietary intervention improves 2-hr oral glucose tolerance in individuals with prediabetes. However, the improvements in glucose homeostasis with RT appear limited to those with IGT or combined IFG and IGT.

Trial Registration

ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01112709","term_id":"NCT01112709"}}NCT01112709     

Fasting Plasma Glucose as Initial Screening for Diabetes and Prediabetes in Irish Adults: The Diabetes Mellitus and Vascular Health Initiative (DMVhi)

Objective

Type 2 diabetes has a long pre clinical asymptomatic phase. Early detection may delay or arrest disease progression. The Diabetes Mellitus and Vascular health initiative (DMVhi) was initiated as a prospective longitudinal cohort study on the prevalence of undiagnosed Type 2 diabetes and prediabetes, diabetes risk and cardiovascular risk in a cohort of Irish adults aged 45-75 years.

Research Design and Methods

Members of the largest Irish private health insurance provider aged 45 to 75 years were invited to participate in the study. Exclusion criteria: already diagnosed with diabetes or taking oral hypoglycaemic agents. Participants completed a detailed medical questionnaire, had weight, height, waist and hip circumference and blood pressure measured. Fasting blood samples were taken for fasting plasma glucose (FPG). Those with FPG in the impaired fasting glucose (IFG) range had a 75gm oral glucose tolerance test performed.

Results

122,531 subjects were invited to participate. 29,144 (24%) completed the study. The prevalence of undiagnosed diabetes was 1.8%, of impaired fasting glucose (IFG) was 7.1% and of impaired glucose tolerance (IGT) was 2.9%. Dysglycaemia increased among those aged 45-54, 55-64 and 65-75 years in both males (10.6%, 18.5%, 21.7% respectively) and females (4.3%, 8.6%, 10.9% respectively). Undiagnosed T2D, IFG and IGT were all associated with gender, age, blood pressure, BMI, abdominal obesity, family history of diabetes and triglyceride levels. Using FPG as initial screening may underestimate the prevalence of T2D in the study population.

Conclusions

This study is the largest screening study for diabetes and prediabetes in the Irish population. Follow up of this cohort will provide data on progression to diabetes and on cardiovascular outcomes.     

Sedentary behavior, recreational physical activity, and 7-year weight gain among postmenopausal U.S. women

Objective: To assess the relationship among recreational physical activity (PA), non‐occupational sedentary behavior, and 7‐year weight gain among postmenopausal U.S. women 40 to 69 years old. Research Methods and Procedures: In 1992 and 1999, 18,583 healthy female participants from the Cancer Prevention Study II Nutrition Cohort completed questionnaires on anthropometric characteristics and lifestyle factors. The associations between recreational PA [in metabolic equivalent (MET) hours per week] and non‐occupational sedentary behavior (in hours per day) at baseline and risk for 7‐year weight gain (5 to 9 or ≥10 vs. ±4 pounds) were assessed using multivariate logistic regression analysis. Results: Neither PA nor sedentary behavior was associated with a 5‐ to 9‐pound weight gain. Among women who were not overweight at baseline (BMI <25.0), the odds of ≥10‐pound weight gain were 12% lower (odds ratio, 0.88; 95% confidence interval, 0.77 to 0.99) for those in the highest category of recreational PA (≥18 MET h/wk) compared with >0 to <4 MET h/wk; odds were 47% higher (odds ratio, 1.47; 95% confidence interval, 1.21 to 1.79) for non‐overweight women who reported ≥6 h/d of non‐occupational sedentary behavior compared with <3 h/d. Neither PA nor sedentary behavior were associated with risk of ≥10‐pound weight gain weight among women who were overweight at baseline (BMI ≥25.0). Discussion: Both recreational PA and non‐occupational sedentary behavior independently predicted risk of ≥10‐pound weight gain among postmenopausal women who were not overweight at baseline. Public health messages to prevent weight gain among normal‐weight postmenopausal women may need to focus on decreasing time spent in sedentary behaviors and increasing the amount of time spent on PA.     

Effects of Obesity on the Conversion from Normal Glucose Tolerance to Diabetes in Hong Kong Chinese

Objective: To assess the effects of BMI on progression to diabetes in Hong Kong Chinese and to analyze the optimal cutoff for overweight and obesity in Hong Kong Chinese. Research Methods and Procedures: This is a prospective study with a mean follow‐up of 2.1 years (median 1.4 years, range 0.9 to 8.4 years). We recruited 172 nondiabetic high‐risk subjects, of whom 115 had normal glucose tolerance (NGT) and 57 had impaired glucose tolerance (IGT). BMI and 75‐gram oral glucose tolerance tests were assessed at baseline and then at yearly intervals Results: The crude rates of progression to diabetes for subjects with NGT or IGT were 8.4% and 11.5% per year, respectively. For subjects with NGT, the progression rate to diabetes differed with different BMI ranges. For subjects with NGT and BMI ≥ 25 kg/m², the crude rates of progression to diabetes or glucose intolerance (diabetes or IGT) were 12.5% per year and 14.6% per year, respectively. The corresponding rates for subjects with NGT and BMI ≥ 28 kg/m² were 14.6% and 18.9% per year, respectively. Among subjects with NGT, those with BMI between 25 and 28 kg/m² had the highest Youden index and likelihood ratio to predict the conversion to diabetes or glucose intolerance. Discussion: Obese subjects with NGT had higher rates of progression to diabetes than nonobese subjects. We recommend redefining BMI cutoffs, with 23 kg/m² for overweight and 28 kg/m² for obesity. This definition may be more sensitive to identify at‐risk subjects and more specific to identify “patients” for therapeutic management.     

Associations of Green Tea and Rock Tea Consumption with Risk of Impaired Fasting Glucose and Impaired Glucose Tolerance in Chinese Men and Women

Objective

To explore the associations of green tea and rock tea consumption with risk of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT).

Methods

A multistage, stratified, cluster, random-sampling method was used to select a representative sample from Fujian Province in China. In total, 4808 subjects without cardiovascular disease, hypertension, cancer, or pancreatic, liver, kidney, or gastrointestinal diseases were enrolled in the study. A standard questionnaire was used to gather data on tea (green, rock, and black) consumption and other relevant factors. The assessment of impaired glucose regulation (IGR) was using 75-g oral glucose tolerance test (OGTT), the diagnostic criteria of normal glucose tolerance was according to American Diabetes Association.

Results

Green tea consumption was associated with a lower risk of IFG, while rock tea consumption was associated with a lower risk of IGT. The adjusted odds ratios for IFG for green tea consumption of <1, 1–15, 16–30, and >30 cups per week were 1.0 (reference), 0.42 (95% confidence intervals (CI) 0.27–0.65), 0.23 (95% CI, 0.12–0.46), and 0.41 (95% CI, 0.17–0.93), respectively. The adjusted odds ratios for IGT for rock tea consumption of <1, 1–15, 16–30, and >30 cups per week were 1.0 (reference), 0.69 (95% CI, 0.48–0.98), 0.59 (95% CI, 0.39–0.90), and 0.64 (95% CI, 0.43–0.97), respectively. A U-shaped association was observed, subjects who consumed 16–30 cups of green or rock tea per week having the lowest odds ratios for IFG or IGT.

Conclusions

Consumption of green or rock tea may protect against the development of type 2 diabetes mellitus in Chinese men and women, particularly in those who drink 16–30 cups per week.     

Adipokine pattern in subjects with impaired fasting glucose and impaired glucose tolerance in comparison to normal glucose tolerance and diabetes

Aim

Altered adipokine serum concentrations early reflect impaired adipose tissue function in obese patients with type 2 diabetes (T2D). It is not entirely clear whether these adipokine alterations are already present in prediabetic states and so far there is no comprehensive adipokine panel available. Therefore, the aim of this study was to assess distinct adipokine profiles in patients with normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or T2D.

Methods

Based on 75 g oral glucose tolerance tests, 124 individuals were divided into groups of IFG (n = 35), IGT (n = 45), or NGT (n = 43). Furthermore, 56 subjects with T2D were included. Serum concentrations of adiponectin, chemerin, fetuin-A, leptin, interleukin (IL)-6, retinol-binding protein 4 (RBP4), monocyte chemoattractant protein (MCP)-1, vaspin, progranulin, and soluble leptin receptor (sOBR) were measured by ELISAs.

Results

Chemerin, progranulin, fetuin-A, and RBP4, IL-6, adiponectin and leptin serum concentrations were differentially regulated among the four investigated groups but only circulating chemerin was significantly different in patients with IGT compared to those with IFG. Compared to T2D the IFG subjects had higher serum chemerin, progranulin, fetuin-A and RBP4 levels which was not detectable in the comparison of the T2D and IGT group.

Conclusion

Alterations in adipokine serum concentrations are already detectable in prediabetic states, mainly for chemerin, and may reflect adipose tissue dysfunction as an early pathogenetic event in T2D development. In addition, distinct adipokine serum patterns in individuals with IFG and IGT suggest a specific role of adipose tissue in the pathogenesis of these prediabetic states.     

Discordant risk: Overweight and cardiometabolic risk in Chinese adults

Objective:

Recent US work identified “metabolically healthy overweight” and “metabolically at risk normal weight” individuals. Less is known for modernizing countries with recent increased obesity.

Design and Methods:

Fasting blood samples, anthropometry and blood pressure from 8,233 adults aged 18‐98 in the 2009 nationwide China Health and Nutrition Survey, were used to determine prevalence of overweight (Asian cut point, BMI ≥23 kg/m²) and five risk factors (prediabetes/diabetes (hemoglobin A1c ≥5.7%) inflammation (high‐sensitivity C‐reactive protein (hsCRP) ≥3 mg/l), prehypertension/hypertension (Systolic blood pressure/diastolic blood pressure≥130/85 mm Hg), high triglycerides (≥150 mg/dl), low high‐density lipoprotein cholesterol (<40 (men)/ <50 mg/dl (women)). Sex‐stratified, logistic, and multinomial logistic regression models estimated concurrent obesity and cardiometabolic risk, with and without abdominal obesity, adjusting for age, smoking, alcohol consumption, physical activity, urbanicity, and income.

Results:

Irrespective of urbanicity, 78.3% of the sample had ≥1 elevated cardiometabolic risk factor (normal weight: 33.2% had ≥1 elevated risk factor; overweight: 5.7% had none). At the age of 18‐30 years, 47.4% had no elevated risk factors, which dropped to 6% by the age 70, largely due to age‐related increase in hypertension risk (18‐30 years: 11%; >70 years: 73%). Abdominal obesity was highly predictive of metabolic risk, irrespective of overweight (e.g., “metabolically at risk overweight” relative to “metabolically healthy normal weight” (men: relative risk ratio (RRR) = 39.06; 95% confidence interval (CI): 23.47, 65.00; women: RRR = 22.26; 95% CI: 17.49, 28.33)).

Conclusion:

A large proportion of Chinese adults have metabolic abnormalities. High hypertension risk with age, underlies the low prevalence of metabolically healthy overweight. Screening for cardiometabolic‐related outcomes dependent upon overweight will likely miss a large portion of the Chinese at risk population.     

Longitudinal associations between BMI,waist circumference,and cardiometabolic risk in US youth: Monitoring implications

Objective:

This study examined whether change in body mass index (BMI) or waist circumference (WC) is associated with change in cardiometabolic risk factors and differences between cardiovascular disease specific and diabetes specific risk factors among adolescents. We also sought to examine any differences by gender or baseline body mass status.

Design:

The article is a longitudinal analysis of pre‐ and post‐data collected in the HEALTHY trial. Participants were 4,603 ethnically diverse adolescents who provided complete data at 6th and 8th grade assessments.

Methods:

The main outcome measures were percent change in the following cardiometabolic risk factors: fasting triglycerides, systolic and diastolic blood pressure, high density lipoprotein cholesterol, and glucose as well as a clustered metabolic risk score. Main exposures were change in BMI or WC z‐score. Models were run stratified by gender; secondary models were additionally stratified by baseline BMI group (normal, overweight, or obese).

Results:

Analysis showed that when cardiometabolic risk factors were treated as continuous variables, there was strong evidence (P < 0.001) that change in BMI z‐score was associated with change in the majority of the cardiovascular risk factors, except fasting glucose and the combined risk factor score for both boys and girls. There was some evidence that change in WC z‐score was associated with some cardiovascular risk factors, but change in WC z‐score was consistently associated with changes in fasting glucose.

Conclusions:

In conclusion, routine monitoring of BMI should be continued by health professionals, but additional information on disease risk may be provided by assessing WC.     

A randomized,phase 3 trial of naltrexone SR/bupropion SR on weight and obesity‐related risk factors (COR‐II)

Objective:

To examine the effects of naltrexone/bupropion (NB) combination therapy on weight and weight‐related risk factors in overweight and obese participants.

Design and Methods:

CONTRAVE Obesity Research‐II (COR‐II) was a double‐blind, placebo‐controlled study of 1,496 obese (BMI 30‐45 kg/m²) or overweight (27‐45 kg/m² with dyslipidemia and/or hypertension) participants randomized 2:1 to combined naltrexone sustained‐release (SR) (32 mg/day) plus bupropion SR (360 mg/day) (NB32) or placebo for up to 56 weeks. The co‐primary endpoints were percent weight change and proportion achieving ≥5% weight loss at week 28.

Results:

Significantly (P < 0.001) greater weight loss was observed with NB32 versus placebo at week 28 (?6.5% vs. ?1.9%) and week 56 (?6.4% vs. ?1.2%). More NB32‐treated participants (P < 0.001) experienced ≥5% weight loss versus placebo at week 28 (55.6% vs. 17.5%) and week 56 (50.5% vs. 17.1%). NB32 produced greater improvements in various cardiometabolic risk markers, participant‐reported weight‐related quality of life, and control of eating. The most common adverse event with NB was nausea, which was generally mild to moderate and transient. NB was not associated with increased events of depression or suicidality versus placebo.

Conclusion:

NB represents a novel pharmacological approach to the treatment of obesity, and may become a valuable new therapeutic option.

     

Impaired Glucose Tolerance or Newly Diagnosed Diabetes Mellitus Diagnosed during Admission Adversely Affects Prognosis after Myocardial Infarction: An Observational Study

Objective

To investigate the prognostic effect of newly diagnosed diabetes mellitus (NDM) and impaired glucose tolerance (IGT) post myocardial infarction (MI).

Research Design and Methods

Retrospective cohort study of 768 patients without preexisting diabetes mellitus post-MI at one centre in Yorkshire between November 2005 and October 2008. Patients were categorised as normal glucose tolerance (NGT n = 337), IGT (n = 279) and NDM (n = 152) on pre- discharge oral glucose tolerance test (OGTT). Primary end-point was the first occurrence of major adverse cardiovascular events (MACE) including cardiovascular death, non-fatal MI, severe heart failure (HF) or non-haemorrhagic stroke. Secondary end-points were all cause mortality and individual components of MACE.

Results

Prevalence of NGT, impaired fasting glucose (IFG), IGT and NDM changed from 90%, 6%, 0% and 4% on fasting plasma glucose (FPG) to 43%, 1%, 36% and 20% respectively after OGTT. 102 deaths from all causes (79 as first events of which 46 were cardiovascular), 95 non fatal MI, 18 HF and 9 non haemorrhagic strokes occurred during 47.2 ± 9.4 months follow up. Event free survival was lower in IGT and NDM groups. IGT (HR 1.54, 95% CI: 1.06–2.24, p = 0.024) and NDM (HR 2.15, 95% CI: 1.42–3.24, p = 0.003) independently predicted MACE free survival. IGT and NDM also independently predicted incidence of MACE. NDM but not IGT increased the risk of secondary end-points.

Conclusion

Presence of IGT and NDM in patients presenting post-MI, identified using OGTT, is associated with increased incidence of MACE and is associated with adverse outcomes despite adequate secondary prevention.     

Central adiposity and other anthropometric factors in relation to risk of macrosomia in an african american population

Objective:

Previous studies have consistently identified maternal obesity and gestational weight gain (GWG) as risk factors for macrosomia, but little is known about the effects of central adiposity and body fat distribution. Using self‐reported data from the Black Women's Health Study (BWHS), a large follow‐up study of US black women, we examined the risk of macrosomia in relation to prepregnancy waist circumference, prepregnancy waist‐to‐hip ratio (WHR), prepregnancy BMI, and GWG.

Design and Methods:

During 1995–2003, BWHS participants ages 21–44 years delivered 6,687 full‐term singleton births (gestational age >37 weeks). We compared mothers of 691 infants weighing ≥4,000 g with mothers of 5,996 infants weighing <4,000 g. Generalized estimating equation models (GEE) that accounted for more than one birth per mother were used to estimate multivariable odds ratios (OR) and 95% confidence intervals (CI).

Results:

Independent of prepregnancy BMI, prepregnancy waist circumference was positively associated with risk of macrosomia (OR = 1.58, 95% CI: 1.07–2.32, for ≥35.0 vs. <27.0 inches (≥88.9 vs. <68.6 cm); P trend = 0.04). As expected, prepregnancy BMI was also positively associated with macrosomia (OR = 1.74, 95% CI: 1.25–2.41 for BMI ≥35.0 vs. 18.5–24.9 kg m^?2). GWG above the amount recommended by the 2009 Institute of Medicine report was associated with an increased risk of macrosomia and the association was present in each category of prepregnancy BMI (18.5–24.9, 25.0–29.9, and ≥30.0 kg m^?2; P trend <0.001).

Conclusions:

Our data suggest that overall obesity, high GWG, and high waist circumference are independent risk factors for macrosomia among US black women.

     

Circulating regulatory T cells are reduced in obesity and may identify subjects at increased metabolic and cardiovascular risk

Objective:

Reduced numbers of regulatory T (T_reg) cells have been observed in visceral adipose tissue of obese mice and humans. However, it is unknown whether human obesity affects circulating Treg cells and whether their number is associated with markers of systemic inflammation or glucose intolerance.

Design and Methods:

Peripheral blood mononuclear cells were isolated from venous blood of obese (BMI ≥ 27 kg/m²; n = 30) and nonobese (BMI ≥ 27 kg/m²; n = 13) individuals and analyzed using flow cytometry for the expression of CD4, CD25, and Foxp3.

Results:

Reduced circulating T_reg‐cell numbers were detected in obese compared with nonobese study participants (P = 0.038). Circulating CD4⁺CD25⁺CD127^?Foxp3 T_reg cells inversely correlated with body weight (P = 0.009), BMI (P = 0.004) and plasma leptin levels (P = 0.004) and were reduced in subjects with hsCRP ≥ 3.0 mg/L (P = 0.034) or HbA1c ≥ 5.5% (P < 0.005). Receiver operating characteristic curve analysis revealed a cutoff of circulating Treg cells < 1.06% to be predictive for hsCRP levels ≥ 3.0 mg/L, and logistic regression showed that the risk of having hsCRP levels ≥ 3.0 mg/L was increased 9.6‐fold (P = 0.008), if T_reg cells were below this threshold. The T_reg cutoff for HbA1c levels ≥ 5.5% was 0.73%, and this cutoff also predicted an increased risk of having elevated levels of both hsCRP and HbA1c, if only obese subjects were examined.

Conclusion:

Our findings thus reveal an association between circulating T_reg cells and measures of adiposity, inflammation, and glucose intolerance. Although further prospective studies are needed, we present data suggesting that the determination of T_reg cells might be useful to identify obese subjects at increased risk of developing cardiovascular and/or metabolic complications.

     

Association between markers of fatty liver disease and impaired glucose regulation in men and women from the general population: the KORA-F4-study

Objective

To investigate whether the elevated liver enzymes gamma-glutamyltransferase (GGT), glutamate-pyruvate transaminase (GPT), glutamate-oxalacetate transaminase (GOT) and alkaline phosphatase (AP) and non-alcoholic fatty liver disease (NAFLD) respectively are independently associated with pre-diabetic states, namely impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) or known and newly diagnosed diabetes (NDD), in men and women from the general German population.

Methods

The study was based on 3009 subjects (1556 females, 1453 males) aged 32 to 81 years who participated in the KORA-F4-Study in 2006/2008 in Augsburg, Southern Germany. All non-diabetic participants underwent an oral glucose tolerance test to assess disturbances in glucose metabolism. NAFLD was estimated by liver enzyme concentrations and the Bedogni Fatty Liver Index (FLI).

Results

229 participants (7.6%) reported known diabetes, 106 had NDD (3.5%), 107 (3.6%) had IFG, 309 (10.3%) had IGT, 69 (2.3%) were affected with both metabolic disorders (IFG/IGT) and 74 (2.5%) could not be classified. GGT and GPT were significantly elevated in persons with pre-diabetes and diabetes (GGT in diabetic persons OR = 1.76, [1.47–2.09], in IFG OR = 1.79 [1.50–2.13], GPT in diabetic persons OR = 1.51, [1.30–1.74], in NDD OR = 1.77 [1.52–2.06]), GOT and AP only inconsistently in some pre-diabetes groups. The effects were sharpened in models using an increase of two or three out of three enzymes as an estimate of fatty liver and especially in models using the FLI. Overall frequency of NAFLD applying the index was 39.8% (women: 27.3% and men: 53.2%). In participants with fatty liver disease, the OR for NDD adjusted for sex and age was 8.48 [5.13–14.00], 6.70 [3.74–12.01] for combined IFG and IGT and 4.78 [3.47–6.59] for known diabetes respectively.

Conclusions

Elevated GGT and GPT–values as well as estimates of fatty liver disease are significantly associated with pre-diabetes and diabetes and thus very useful first indicators of a disturbed glucose metabolism.     

Extremely short duration high intensity interval training substantially improves insulin action in young healthy males

Background

Impaired glucose tolerance (IGT) is a prediabetic state. If IGT can be prevented from progressing to overt diabetes, hyperglycemia-related complications can be avoided. The purpose of the present study was to examine whether pioglitazone (ACTOS^®) can prevent progression of IGT to type 2 diabetes mellitus (T2DM) in a prospective randomized, double blind, placebo controlled trial.

Methods/Design

602 IGT subjects were identified with OGTT (2-hour plasma glucose = 140–199 mg/dl). In addition, IGT subjects were required to have FPG = 95–125 mg/dl and at least one other high risk characteristic. Prior to randomization all subjects had measurement of ankle-arm blood pressure, systolic/diastolic blood pressure, HbA_1C, lipid profile and a subset had frequently sampled intravenous glucose tolerance test (FSIVGTT), DEXA, and ultrasound determination of carotid intima-media thickness (IMT). Following this, subjects were randomized to receive pioglitazone (45 mg/day) or placebo, and returned every 2–3 months for FPG determination and annually for OGTT. Repeat carotid IMT measurement was performed at 18 months and study end. Recruitment took place over 24 months, and subjects were followed for an additional 24 months. At study end (48 months) or at time of diagnosis of diabetes the OGTT, FSIVGTT, DEXA, carotid IMT, and all other measurements were repeated. Primary endpoint is conversion of IGT to T2DM based upon FPG ≥ 126 or 2-hour PG ≥ 200 mg/dl. Secondary endpoints include whether pioglitazone can: (i) improve glycemic control (ii) enhance insulin sensitivity, (iii) augment beta cell function, (iv) improve risk factors for cardiovascular disease, (v) cause regression/slow progression of carotid IMT, (vi) revert newly diagnosed diabetes to normal glucose tolerance.

Conclusion

ACT NOW is designed to determine if pioglitazone can prevent/delay progression to diabetes in high risk IGT subjects, and to define the mechanisms (improved insulin sensitivity and/or enhanced beta cell function) via which pioglitazone exerts its beneficial effect on glucose metabolism to prevent/delay onset of T2DM.

Trial Registration

clinical trials.gov identifier: NCT00220961     

Regional Differences of Undiagnosed Type 2 Diabetes and Prediabetes Prevalence Are Not Explained by Known Risk Factors

Background

We have previously found regional differences in the prevalence of known type 2 diabetes between northeastern and southern Germany. We aim to also provide prevalence estimates for prediabetes (isolated impaired fasting glucose (i-IFG), isolated glucose intolerance (i-IGT), combined IFG and IGT) and unknown type 2 diabetes for both regions.

Methods

Prevalence (95%CI) of prediabetes (i-IFG: fasting glucose 5.6–6.9 mmol/l; i-IGT: 2 h postchallenge gluose 7.8–11.0 mmol/l, oral glucose tolerance test (OGTT), ≥8 h overnight fasting) and unknown diabetes were analyzed in two regional population-based surveys (age group 35–79 years): SHIP-TREND (Study of Health in Pomerania (northeast), 2008–2012) and KORA F4 (Cooperative Health Research in the region of Augsburg (south), 2006–2008). Both studies used similar methods, questionnaires, and identical protocols for OGTT. Overall, 1,980 participants from SHIP-TREND and 2,617 participants from KORA F4 were included.

Results

Age-sex-standardized prevalence estimates (95%CI) of prediabetes and unknown diabetes were considerably higher in the northeast (SHIP-TREND: 43.1%; 40.9–45.3% and 7.1%; 5.9–8.2%) than in the south of Germany (KORA F4: 30.1%; 28.4–31.7% and 3.9%; 3.2–4.6%), respectively. In particular, i-IFG (26.4%; 24.5–28.3% vs. 17.2%; 15.7–18.6%) and IFG+IGT (11.2%; 9.8–12.6% vs. 6.6%; 5.7–7.5%) were more frequent in SHIP-TREND than in KORA. In comparison to normal glucose tolerance, the odds of having unknown diabetes (OR, 95%CI: 2.59; 1.84–3.65) or prediabetes (1.98; 1.70–2.31) was higher in the northeast than in the south after adjustment for known risk factors (obesity, lifestyle).

Conclusions

The regional differences of prediabetes and unknown diabetes are in line with the geographical pattern of known diabetes in Germany. The higher prevalences in the northeast were not explained by traditional risk factors.     

Racial/ethnic differences in the prevalence of gestational diabetes mellitus and maternal overweight and obesity,by Nativity,Florida, 2004‐2007

Objective:

We examined the risk of gestational diabetes mellitus (GDM) among foreign‐born and U.S.‐born mothers by race/ethnicity and BMI category.

Design and Method:

We used 2004‐2007 linked birth certificate and maternal hospital discharge data of live, singleton deliveries in Florida to compare GDM risk among foreign‐born and U.S.‐born mothers by race/ethnicity and BMI category. We examined maternal BMI and controlled for maternal age, parity, and height.

Results:

Overall, 22.4% of the women in our study were foreign born. The relative risk (RR) of GDM among women who were overweight or obese (BMI ≥ 25.0 kg m^?2) was higher than among women with normal BMI (18.5‐24.9 kg m^?2) regardless of nativity, ranging from 1.3 (95% confidence interval (CI) = 1.0, 1.9) to 3.8 (95% CI = 2.1, 7.2).Foreign‐born women also had a higher GDM risk than U.S.‐born women, with RR ranging from 1.1 (95% CI = 1.1, 1.2) to 2.1 (95% CI = 1.4, 3.1). This finding was independent of BMI, age, parity, and height for all racial/ethnicity groups.

Conclusions:

Although we found differences in age, parity, and height by nativity, these differences did not substantially reduce the increased risk of GDM among foreign‐born mothers. Health practitioners should be aware of and have a better understanding of how race/ethnicity and nativity can affect women with a high risk of GDM. Although BMI is a major risk factor for GDM, it does not appear to be associated with race/ethnicity or nativity.

     

Adiposity,blood pressure,and carotid intima‐media thickness in greek adolescents

Objective:

In children and adolescents with cardiovascular risk factors, the assessment of subclinical target‐organ damage is of paramount importance. This study investigated factors associated with carotid intima‐media thickness (cIMT) in adolescents.

Design and Methods:

A cross‐sectional study was performed in 448 apparently healthy adolescents recruited from schools (mean age 14 ± 2.2 years, 211 boys), which involved cIMT measurements (common carotid artery) and assessment of lipid profile, glucose, and blood pressure (BP).

Results:

The prevalence of overweight/obesity was 28.1%/12.7% and of BP ≥95th percentile 19.6%. Left cIMT was correlated with age (r = 0.10), waist circumference (WC) (0.15), and BP (0.21/0.13, systolic/diastolic) (all P < 0.05). Right cIMT was correlated with waist to hip ratio (WHR) (0.10), whereas the mean of left and right cIMT was correlated with WC (0.12), WHR (0.12), and systolic BP (0.14) (all P < 0.05). After the age of 13 years, boys tended to have higher cIMT than girls, which was significant in the 13‐15 years subgroup (P < 0.05). In stepwise multivariate analysis (independent variables: age, gender, WC, WHR, body mass index z‐score, lipid parameters, glucose, BP), left cIMT was independently associated with systolic BP; right cIMT with WHR; mean left and right cIMT with WC. Adolescents with BP ≥90th percentile had higher left cIMT than those <90th percentile (0.63 ± 0.09 vs. 0.61 ± 0.09 mm respectively, P < 0.05).

Conclusion:

Central adiposity and systolic BP appear to be independently associated with increased cIMT values in apparently healthy adolescents. Left side cIMT appears to be superior to right side measurements in terms of association with cardiovascular risk factors.