Insulin analogs as an add-on to metformin after failure to oral treatment in type 2 diabetic patients increase diastole duration. The INSUlin Regimens and VASCular Functions (INSUVASC) study.

BACKGROUND: Fast acting insulin analogues are known to improve arterial stiffness. The combination of metformin with insulin represents a widely used therapeutic strategy in diabetes. We hypothesized that insulin treatment in patients with type 2 diabetes (T2D) with long-acting, fast-acting or basal bolus insulin as an add-on to metformin would provide additional improvement of arterial stiffness. METHODS: The INSUlin Regimens and VASCular Functions (INSUVASC) study is a pilot, randomized, open label three-arms study that included 42 patients with type 2 diabetes (T2D) in primary prevention, after a failure to oral antidiabetic agents. Arterial stiffness measurements were performed at fasting and after a standardized breakfast. During the first visit (V1) pre-randomization, participants took only metformin to perform the tests. The same tests were repeated after 4 weeks of insulin treatment during the second visit (V2). RESULTS: Data were available for final analysis in 40 patients, with a mean age of 53.6±9.7 years and a mean duration of diabetes of 10.6±5.6 years. Twenty-one were females (52.5%), hypertension and dyslipidemia were present in 18 (45%) and 17 patients (42.5%), respectively. After insulin treatment, the metabolic control was associated to a decrease in oxidative stress and improvement of endothelial functions, with a post prandial diastole duration increased and a decrease of the peripheral arterial stiffness, with a better post prandial pulse pressure ratio and ejection duration after insulin. In hypertensive patients, insulin treatment provided positive effects by decreasing the pulse wave velocity and improving reflection time. CONCLUSIONS: A short time treatment by insulin in addition to metformin improved myocardial perfusion. Moreover, insulin treatment in hypertensive patients provides a better hemodynamic profile in large arteries.

Asymptomatic left ventricular dysfunction in patients with type 2 diabetes free of cardiovascular disease and its relationship with clinical characteristics: The DIACAR cohort study.

AIMS: To assess the prevalence, type and clinical factors associated with left ventricular (LV) dysfunction in patients with type 2 diabetes mellitus (T2DM) by performing a comprehensive echocardiographic Doppler assessment including speckle tracking. METHODS: Two hundred T2DM patients without overt cardiovascular disease were prospectively enrolled in a single-centre cohort study between 2018 and 2019. RESULTS: Left ventricular mass was increased in 24 patients (12%) and relative wall thickness (h/r) was increased in 46 patients (23%). Left atrial (LA) enlargement was observed in 27 patients (13.6%) and global longitudinal strain (GLS) was reduced in 38 patients (20.3%). In univariate analysis, LV hypertrophy (LVH) or increased h/r were associated with age, renal function, hypertension and B-type natriuretic peptide (BNP) plasma level. LA dilation was associated with age, history of hypertension, diabetes duration and complications, insulin treatment, BNP level and renal function. GLS was associated with body mass index (BMI) and, in a borderline manner, with diabetes duration. In multivariate analysis, hypertension was associated with LVH and with h/r and a borderline relationship was observed for female gender (LVH), age and insulin treatment (h/r). Age, hypertension and, in a borderline manner, insulin treatment were associated with LA dilation. BMI and shorter diabetes duration were associated with reduced GLS. CONCLUSION: A high prevalence of asymptomatic cardiac dysfunction/structural abnormalities was observed in patients with T2DM without overt cardiac disease and was associated with either age, diabetes duration or treatment and with comorbidities including hypertension and obesity. Whether these preclinical abnormalities are associated with poor outcomes warrants further study.

Poor Reliability and Poor Adherence to Self-Monitoring of Blood Glucose Are Common in Women With Gestational Diabetes Mellitus and May Be Associated With Poor Pregnancy Outcomes.

OBJECTIVE: To evaluate the compliance with self-monitoring of blood glucose (SMBG) and the reliability of diabetes logbooks in women with gestational diabetes mellitus (GDM), as well as the associated determinants and outcomes. RESEARCH DESIGN AND METHODS: We prospectively selected French-speaking women with newly diagnosed GDM who had been referred to our diabetes management program and understood SMBG principles. At the next follow-up visit, we collected SMBG results from glucose meters and logbooks. We analyzed pregnancy outcomes. RESULTS: Data were analyzed over 13 ± 3 days in 91 women. Only 61.5% had performed ≥80% of the required tests. Poor compliance was associated with a family history of diabetes, social deprivation, and non-European origin. The average time between pre- and postprandial tests was 141 ± 20 min, with 46.5% of women performing ≥80% of postprandial measurements 100-140 min after meals. Inadequate timing was associated with ethnicity and higher HbA1c at baseline. A total of 23.1% of women had <90% matched values in diary and meter memory, and a poor concordance was associated with a family history of diabetes. Poor adherence was associated with more preeclampsia (12.2 vs. 1.9%, P = 0.049), and inadequate postprandial test timing with a higher HbA1c at delivery (5.3 ± 0.4 vs. 5.0 ± 0.3% [34 ± 2 vs. 31 ± 2 mmol/mol], P < 0.01), despite more frequent insulin therapy. CONCLUSIONS: Although women with GDM are considered to be highly motivated, SMBG adherence and reliability are of concern and may be associated with poor gestational prognosis, suggesting that caregivers should systematically check the glucose meter memory to improve GDM management.

Evidence for a Specific Diabetic Cardiomyopathy: An Observational Retrospective Echocardiographic Study in 656 Asymptomatic Type 2 Diabetic Patients.

Aim. Our aim was to assess the prevalence of subclinical diabetic cardiomyopathy, occurring among diabetic patients without hypertension or coronary artery disease (CAD). Methods. 656 asymptomatic patients with type 2 diabetes for 14 ± 8 years (359 men, 59.7 ± 8.7 years old, HbA1c 8.7 ± 2.1%) and at least one cardiovascular risk factor had a cardiac echography at rest, a stress cardiac scintigraphy to screen for silent myocardial ischemia (SMI), and, in case of SMI, a coronary angiography to screen for silent CAD. Results. SMI was diagnosed in 206 patients, and 71 of them had CAD. In the 157 patients without hypertension or CAD, left ventricular hypertrophy (LVH: 24.1%) was the most frequent abnormality, followed by left ventricular dilation (8.6%), hypokinesia (5.3%), and systolic dysfunction (3.8%). SMI was independently associated with hypokinesia (odds ratio 14.7 [2.7-81.7], p < 0.01) and systolic dysfunction (OR 114.6 [1.7-7907], p < 0.01), while HbA1c (OR 1.9 [1.1-3.2], p < 0.05) and body mass index (OR 1.6 [1.1-2.4], p < 0.05) were associated with systolic dysfunction. LVH was more prevalent among hypertensive patients and hypokinesia in the patients with CAD. Conclusion. In asymptomatic type 2 diabetic patients, diabetic cardiomyopathy is highly prevalent and is predominantly characterized by LVH. SMI, obesity, and poor glycemic control contribute to structural and functional LV abnormalities.

Increased glycemic variability and decrease of the postprandial glucose contribution to HbA1c in obese subjects across the glycemic continuum from normal glycemia to first time diagnosed diabetes.

OBJECTIVE: The contribution of postprandial glycemia (PPG) to hyperglycemia has been shown to decrease as HbA1c increased in type 2 diabetic patients. This study aimed at examining, in a series of overweight/obese patients without known glycemic disorder, the contribution of PPG to a "relative" hyperglycemia (glucose values≥5.5 mmol/L) and the presence of glycemic variability according to HbA1c levels. METHODS: Seventy overweight/obese inpatients (body mass index 35.2±6.8 kg/m2) without known glycemic disorder were included. Participants were classified according to an oral glucose tolerance test (according to the American Diabetes Association criteria) as patients with normoglycemia (n=33), with intermediate hyperglycemia (n=24) or diabetes (n=13). They were separated into HbA1c quartiles (Q1 to Q4). A 24 hour continuous glucose monitoring was used under a 1800 kcal diet and minimal physical activity. We assessed PPG contribution (3 hour period after each meal) to the "relative" 24 hour hyperglycemia (glucose values ≥5.5 mmol/L); the remaining time was considered as the fasting/post-absorptive period. RESULTS: HbA1c range was from 5.1% to 7.4% (32 to 57 mmol/mmol). From the lowest to the highest HbA1c quartile, the area under the curve (AUC) for the "relative" hyperglycemia presented a 17-fold increase for the fasting/post-absorptive (p<0.001) period and a 7-fold increase postprandially (p<0.001). The percent of PPG contribution to the "relative" hyperglycemia was calculated with the following formula [100×(postprandial 3 hour AUC-3 h AUC for a constant 5.5 mmol/L glycemia)/(total 24 h AUC-24 h AUC for constant 5. 5 mmol/L glycemia)] and decreased from Q1 to Q4 of HbA1c (81.2%, 66%, 65.8%, 57%; p<0.001). Increasing HbA1c quartiles were associated with higher daily mean blood glucose level (p<0.001) and higher levels of daily glucose variability indices, including mean amplitude of glycemic excursions (p<0.01). CONCLUSIONS: In overweight/obese patients, HbA1c was associated with lower PPG contribution to "relative" hyperglycemia and greater glycemic variability. The present findings support the importance of postprandial period in glycemic exposure even before the appearance of diabetes.

The diagnostic and prognostic performance of a selective screening strategy for gestational diabetes mellitus according to ethnicity in Europe.

CONTEXT: The performance of standard selective screening strategies for gestational diabetes mellitus (GDM) may vary according to ethnicity. OBJECTIVE: We aimed to evaluate the diagnostic and prognostic performance of a selective screening tool to determine whether it accurately predicts GDM and events in women of different ethnicities. The tool selectively screens based on patients having one or more of the following risk factors (RFs): body mass index ≥25 kg/m(2), age ≥35 years, family history of diabetes, and personal history of GDM or macrosomia. DESIGN AND SETTING: We conducted an observational prospective study at a university hospital. PARTICIPANTS: We included 17 344 women of European (30.9%), North African (29.6%), Sub-Saharan African (22.2%), Caribbean (8.7%), Indian-Pakistani-Sri Lankan (5.5%), and Asian (3.3%) ethnicities who were without pregravid diabetes and had singleton deliveries (2002-2010). MAIN OUTCOME MEASURES: We universally screened GDM and GDM-related events (pre-eclampsia, birth weight ≥4000 g, or dystocia). RESULTS: Independent of confounding factors, North African (odds ratio [OR], 1.35; 95% confidence interval [CI], 1.21-1.52; P < .001) and Indian-Pakistani-Sri Lankan (OR, 2.52; 95% CI, 2.13-3.00; P < .001) women had more GDM than Europeans, whereas Sub-Saharan African women had less (OR, 0.82; 95% CI, 0.71-0.94; P < .01). Having one or more RFs was associated with GDM among Europeans (OR, 1.45; 95% CI, 1.22-1.76), North African (OR, 1.33; 95% CI, 1.13-1.55), Sub-Saharan African (OR, 1.48; 95% CI, 1.20-1.83), and Caribbean (OR, 1.55; 95% CI, 1.12-2.14) women. Having one or more RFs was also associated with GDM-related events only in European (P < .01) and North African (P < .05) women, with the following incidences in Europeans: no GDM/no RF, 6.9%; no GDM/RF, 9.0%; GDM/no RF, 14.7%; and GDM/RF, 12.6%. CONCLUSION: Standard selective screening criteria were not predictive of GDM in women from India-Pakistan-Sri Lanka and Asia and were associated with GDM-related events only in European and North African women. However, the women with GDM, who were routinely treated, had a poor prognosis, even for those free of RFs. These results support universal screening, irrespective of ethnicity.

Glycation gap is associated with macroproteinuria but not with other complications in patients with type 2 diabetes.

OBJECTIVE: We investigated whether glycation gap (G-Gap), an index of intracellular glycation of proteins, was associated with diabetes complications. RESEARCH DESIGN AND METHODS: We measured concomitantly HbA1c and fructosamine in 925 patients with type 2 diabetes to calculate the G-Gap, defined as the difference between measured HbA1c, and fructosamine-based predicted HbA1c. Patients were explored for retinopathy, nephropathy, peripheral neuropathy, cardiac autonomic neuropathy (n = 512), and silent myocardial ischemia (n = 506). RESULTS: Macroproteinuria was the only complication that was associated with G-Gap (prevalence in the first, second, and third tertile of G-Gap: 2.9, 6.2, and 11.0%, respectively; P < 0.001). The G-Gap was higher in patients with macroproteinuria than in those without (1.06 ± 1.62 vs. 0.03 ± 1.30%; P < 0.0001). Because HbA1c was associated with both G-Gap (HbA1c 7.0 ± 1.4, 7.9 ± 1.4, and 10.1 ± 1.8% in the first, second, and third G-Gap tertile, respectively; P < 0.0001) and macroproteinuria (HbA1c 8.8 ± 2.2% if macroproteinuria, 8.3 ± 2.0% if none; P < 0.05), and because it could have been a confounder, we matched 54 patients with macroproteinuria and 200 patients without for HbA1c. Because macroproteinuria was associated with lower serum albumin and fructosamine levels, which might account for higher G-Gap, we calculated in this subpopulation albumin-indexed fructosamine and G-Gap; macroproteinuria was independently associated with male sex (odds ratio [OR] 3.2 [95% CI 1.5-6.7]; P < 0.01), hypertension (2.9 [1.1-7.5]; P < 0.05), and the third tertile of albumin-indexed G-Gap (2.3 [1.1-4.4]; P < 0.05) in multivariate analysis. CONCLUSIONS: In type 2 diabetic patients, G-Gap was associated with macroproteinuria, independently of HbA1c, albumin levels, and confounding factors, suggesting a specific role of intracellular glycation susceptibility on kidney glomerular changes.

Cardiovascular risk prediction is improved by adding asymptomatic coronary status to routine risk assessment in type 2 diabetic patients.

OBJECTIVE: To evaluate if silent myocardial ischemia (SMI) and silent coronary artery disease (CAD) provide significant additional value to routine cardiovascular risk assessment in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We followed up to a first cardiovascular event 688 subjects (322 men, aged 59 ± 8 years) out of 731 consecutive asymptomatic type 2 diabetic patients with ≥1 additional risk factor who had been prospectively screened between 1992 and 2006 for SMI by stress myocardial scintigraphy and for silent CAD by coronary angiography. RESULTS: SMI was found in 207 (30.1%) patients and CAD in 76 of those with SMI. Of the patients, 98 had a first cardiovascular event during a 5.4 ± 3.5 (range: 0.1-19.2) year follow-up period. Cox regression analysis considering parameters predicting events but not SMI and CAD ("routine assessment") showed in univariate analyses that macroproteinuria (hazard ratio [HR] 3.33 [95% CI 1.74-6.35]; P < 0.001), current multifactorial care (0.27 [0.15-0.47]; P < 0.001), and peripheral/carotid occlusive arterial disease (PCOAD; 4.33 [2.15-8.71]; P < 0.001) independently predicted cardiovascular events. When added into the model, SMI (HR 1.76 [1.00-3.12]; P = 0.05) and CAD (2.28 [1.24-4.57]; P < 0.01) were also independently associated with events. SMI added to the prediction of an event in the following 5 years above and beyond routine assessment risk prediction (c statistic with or without SMI 0.788 [0.720-0.855] and 0.705 [0.616-0.794], respectively). CONCLUSIONS: Although screening for SMI and silent CAD should not be systematic, these complications are predictive of cardiovascular events in type 2 diabetic patients in addition to routine risk predictors, especially represented by PCOAD, macroproteinuria, and nonintensive management.

Comparison of field methods to estimate fat mass in children.

BACKGROUND: Reliable field methods to measure fat mass (FM) in children may contribute to primary prevention of childhood obesity. AIM: The objective was to compare the accuracy of existing field methods (skinfold thickness (SF), leg-to-leg bioelectrical impedance analysis (BIA), anthropometrics for FM measurement in prepubertal European children. SUBJECTS AND METHODS: Reference FM was measured in 55 French children (30 boys, 25 girls; mean age 8.7 years) using a three-compartment model: body volume (BV) was assessed by air displacement plethysmography (ADP) and total body water (TBW) was assessed by deuterium dilution. Agreement between field methods and the reference method was assessed using Bland-Altman analyses. Since field methods for FM measurement are reported to be population-dependent, adjustment to the study population was performed using stepwise multiple linear regressions modelling. RESULTS: Even after adjustment, field methods exhibited a high correlation (R(2) = 0.71-0.84) but a moderate agreement (+/-3.32 to +/-4.47 kg for fat mass) with the reference model. Methods based on BIA or SF performed slightly better than those based on anthropometry. CONCLUSIONS: Field methods for FM measurement may be recommended for epidemiological applications, but not for individual follow-up. New field equipment is required to improve accuracy of FM measurement in children and make individual follow-up possible.