Reduction in HbA1c with SGLT2 inhibitors vs. DPP-4 inhibitors as add-ons to metformin monotherapy according to baseline HbA1c: A systematic review of randomized controlled trials

AimsThis study compared the reduction of glycated haemoglobin (HbA1c) with sodium-glucose cotransporter type-2 inhibitors (SGLT2is) vs. dipeptidyl peptidase-4 inhibitors (DPP-4is) as add-ons to metformin in patients with type 2 diabetes mellitus (T2DM), with a specific focus on HbA1c changes according to baseline HbA1c.Materials and methodsElectronic databases were scrutinized for randomized controlled trials (RCTs) evaluating the reduction of HbA1c from baseline (Δ HbA1c) with an SGLT2i or DPP-4i in patients with T2DM not well controlled by metformin monotherapy. The endpoint was Δ HbA1c using both indirect and direct comparisons.ResultsOverall, Δ HbA1c was slightly greater with SGLT2is (−0.80 ± 0.20% from 8.03 ± 0.35%; 44 analyses, 29 RCTs, 15 with two doses, n = 9321) than with DPP-4is (−0.71 ± 0.23% from 8.05 ± 0.43%; 61 analyses, 59 RCTs, n = 17,914; P = 0.0354). When the mean baseline HbA1c was < 8% ([64 mmol/mol] 7.79 ± 0.15% vs. 7.71 ± 0.23%), Δ HbA1c averaged −0.735 ± 0.17% vs. −0.62 ± 0.16% (P = 0.0117) with SGLT2is vs. DPP-4is, respectively. However, this difference vanished when the mean baseline HbA1c was ≥ 8% (−0.87 ± 0.22% from 8.27 ± 0.32% with SGLT2is vs. −0.80 ± 0.24% from 8.35 ± 0.33% with DPP-4is; P = 0.2756). The relationship between Δ HbA1c and baseline HbA1c was only slightly stronger with SGLT2is (slope: −0.39, r² = −0.43; P < 0.0001) than with DPP-4is (slope: −0.26, r² = −0.25; P < 0.0001).ConclusionBecause of the small difference in Δ HbA1c whatever the baseline HbA1c level with SGLT2is vs. DPP-4is as add-ons to metformin, choosing between these glucose-lowering agents in clinical practice should be based on other efficacy criteria (such as weight and blood pressure changes, cardiovascular and renal protection) or on safety profiles rather than on HbA1c levels.     

Very-low-energy diet for type 2 diabetes: An underutilized therapy?

BackgroundCurrent approaches to the management of type 2 diabetes focus on the early initiation of novel pharmacologic therapies and bariatric surgery.ObjectiveThe purpose of this study was to revisit the use of intensive, outpatient, behavioral weight management programs for the management of type 2 diabetes.DesignProspective observational study of 66 patients with type 2 diabetes and BMI ≥ 32 kg/m² who enrolled in a program designed to produce 15% weight reduction over 12 weeks using total meal replacement and low- to moderate-intensity physical activity.ResultsPatients were 53 ± 7 years of age (mean ± SD) and 53% were men. After 12 weeks, BMI fell from 40.1 ± 6.6 to 35.1 ± 6.5 kg/m². HbA1c fell from 7.4% ± 1.3% to 6.5% ± 1.2% (57.4 ± 12.3 to 47.7 ± 12.9 mmol/mol) in patients with established diabetes: 76% of patients with established diabetes and 100% of patients with newly diagnosed diabetes achieved HbA1c < 7.0% (53.0 mmol/mol). Improvement in HbA1c over 12 weeks was associated with higher baseline HbA1c and greater reduction in BMI.ConclusionsAn intensive, outpatient, behavioral weight management program significantly improved HbA1c in patients with type 2 diabetes over 12 weeks. The use of such programs should be encouraged among obese patients with type 2 diabetes.     

Utilization of Frontal Assessment Battery and Executive Interview 25 in assessing for dysexecutive syndrome and its association with diabetes self-care in elderly patients with type 2 diabetes mellitus

AimsExecutive function (EF) comprises a set of cognitive skills that controls the execution of complex activities. In the context of diabetes, this may include patients’ self-monitoring and daily management of their condition. We compared two different measures of EF in a population of elderly patients with type 2 diabetes mellitus (T2DM) and studied its relationship with diabetes self-care.MethodsFifty patients (34 males) had EF assessed using Frontal Assessment Battery (FAB) and Executive Interview 25 (EXIT25). Diabetes self-care was assessed using the Summary of Diabetes Self-Care Activities (SDSCA) scale. Haemoglobin A1c (HbA1c), lipid levels, blood pressure and diabetes duration were recorded.ResultsThe mean age of the patients was 67.0 ± 7.5 years and mean duration of diabetes was 8.1 ± 6.4 years. Mean HbA1c was 7.0 ± 1.2%, and mean fasting plasma glucose, cholesterol and LDL-C were 7.0 ± 1.7 mM, 4.0 ± 0.9 mM and 2.1 ± 0.7 mM respectively. Mean EXIT25 score was 9.5 ± 4.6 in the range of normal EF (14% had EXIT25 score > 15, indicating impaired EF). Mean FAB score was 13.7 ± 3.3 (48% having scores < 15, indicating impaired EF), suggesting a degree of dysexecutive syndrome involving frontal lobe functions. EXIT25 score was inversely correlated with SDSCA (r = −0.3, p < 0.05) but no significant correlation between FAB and SDSCA or HbA1c, diabetes duration, lipid levels and blood pressure with EXIT25, FAB or SDCSA was found.ConclusionA substantial proportion of elderly patients with T2DM may have dysexecutive syndrome and impairment in EF may impact on self-care in this group.     

Coeliac autoimmunity in type I diabetes mellitus

Background and study aimsCoeliac autoimmunity (CA) has a known association with type 1 diabetes mellitus (T1DM) for which screening is routinely recommended but less frequently followed. The impact of CA in T1DM has been variably reported. The aims of this study are as follows: (1) to study the prevalence of CA in patients with T1DM and (2) to study the impact of CA not only on nutritional parameters but also on glycaemic control, endocrine axes and bone health.Patients and methodsEighty-six consecutive patients with T1DM were screened for CA using immunoglobulin A (IgA) tissue transglutaminase as a marker (TTG; IgG anti-gliadin in IgA-deficient case). CA positive (CA+) cases were compared with age-matched and sex-matched CA negative (CA−) T1DM cases for anthropometry, glycaemic control (assessed by glycated haemoglobin (HbA1c) and hypoglycaemic/hyperglycaemic episodes), endocrine (thyroid function, cortisol, growth hormone (GH) axis, gonadal axes), haematological (haemoglobin, iron profile and vitamin B₁₂ status) and calcium metabolism parameters and bone densitometry (by dual-energy X-ray absorptiometry (DXA)). Consenting patients with CA also underwent upper gastrointestinal (GI) endoscopy with duodenal biopsy.ResultsOut of 86 patients, 11 (12.75%) screened positive for CA (seven patients underwent duodenal biopsies which were suggestive of Marsh grade III(2), II(3) and I(2) disease). The CA+ T1DM patients were comparable with CA− T1DM in terms of anthropometry. CA+ patients had higher HbA1c (10.7 ± 1.8 vs. 8.4 ± 1.0 (93 ± 19 vs. 68 ± 11 mmol/mol); p < 0.01), more hypoglycaemic episodes (five vs. two; p < 0.05), higher prevalence of iron and vitamin B₁₂ deficiency, lower insulin-like growth factor-1 (IGF-1) levels and lower bone mineral density (BMD) z-score at total body (−1.91 ± 1.05 vs. −0.63 ± 0.73; p < 0.05) and lumbar spine (−1.69 ± 0.92 vs. −0.36 ± 0.93; p < 0.05). The incidence of fractures in the past 3 years was also more in CA+ patients than in CA− patients (four vs. one; p < 0.05).ConclusionCA has an important autoimmune association with T1DM. The concomitant presence of CA adversely affects stature, bone health, glycaemic control and iron and B₁₂ levels in T1DM. IgA sufficiency should be ensured before using an IgA-based screening test for CA.     

Diabetic retinopathy in well-controlled type 2 diabetes: Role of glycaemic memory

AimsAs diabetic retinopathy (DR) can occur even in well-controlled patients with type 2 diabetes (T2D), our study sought to determine whether it might be related to ‘glucose memory’ by evaluating patients’ HbA1c over previous years and their skin autofluorescence (SAF).MethodsIn 334 patients with T2D and HbA1c levels ≤ 8%, their available values of HbA1c from previous years were collected, and their SAF measured by an advanced glycation end-product (AGE) reader. Binary logistic regression analysis was then used to correlate DR with previously recorded HbA1c levels and to SAF, with adjustment for DR risk factors [age, gender, BMI, duration of diabetes, arterial hypertension, diabetic kidney disease (DKD), blood lipid levels and statin treatment].ResultsOur patients were mostly men (58.4%) aged 63 ± 10 years, with a duration of diabetes of 13 ± 10 years and HbA1c = 7.1 ± 0.7%. Of these patients, 84 (25.1%) had DR, which was associated with longer duration of diabetes and greater prevalence of DKD. A total of 605 HbA1c values from previous years were collected for time periods ?4 ± 3 months (n = 255), ?16 ± 4 months (n = 152), ?30 ± 4 months (n = 93) and ?62 ± 26 months (n = 105). After adjustment, the association between DR and having an HbA1c higher than the median was significant only for the oldest previous HbA1c values: OR = 6.75, 95% CI: 1.90–23.90. Moreover, SAF values were higher in those with DR [2.95 ± 0.67 arbitrary units (AU)] vs 2.65 ± 0.65 AU with no DR (P < 0.01) and were also associated with the oldest previous HbA1c values (P < 0.01).ConclusionOur study found that 25.1% of our well-controlled T2D patients had DR, which was related to both their HbA1c levels from 5 years prior to study admission and their SAF values, a marker of glucose memory.     

Association and relative importance of multiple risk factor control on cardiovascular disease,end-stage renal disease and mortality in people with type 2 diabetes: A population-based retrospective cohort study

AimsTo evaluate the risk of cardiovascular disease (CVD), end-stage renal disease (ESRD), and mortality, when implementing a multifactorial optimal control approach in primary care in the United Kingdom (UK), in individuals with newly diagnosed type 2 diabetes.Materials and methodsA retrospective cohort of 53 942 patients were stratified into 1 of the 8 groups according to whether glycated haemoglobin (HbA1c), blood pressure (BP) and total cholesterol (TC) target values were achieved or not from baseline to the date of last follow-up. Those with single or combinations of risk factor control targets achieved, were compared to those who achieved no targets in any of the risk factor. Hazard ratios from the Cox proportional hazards models were estimated against patients who achieved no targets.ResultsOf 53 942 patients with newly diagnosed type 2 diabetes, 28%, 55%, and 68% were at target levels for HbA1c <48 mmol/mol (<6.5%), BP < 140/85 mm Hg, and TC < 5 mmol/L respectively, 36%, 40%, and 12% were at target levels for any one, two, or all three risk factors respectively. Being at HbA1c, BP, and TC targets was associated with an overall 47%, 25%, 42%, 55% and 42% reduction in the risk of ischemic heart disease, cerebrovascular disease, ESRD, cardiovascular-mortality, and all-cause-mortality respectively. Among all subgroups, the risk reduction of study outcome events was greater in the subgroups of patients with microalbuminuria, males, smokers, and patients with BMI ≥ 30 kg/m².ConclusionsOptimal levels of HbA1c, BP, and TC occurring together in patients with newly diagnosed type 2 diabetes are uncommon. Achieving multiple risk factor control targets could substantially reduce the risk of CVD, ESRD and mortality.     

Efficacy of vildagliptin on glucose fluctuation in Japanese type 2 diabetic patients with ongoing sulfonylurea based oral glycemic agent therapy

AimTo investigate whether vildagliptin, one of the dipeptidylpeptide-4 (DDP-4) inhibitors, improves not only glycemic control but also glycemic fluctuation when added to ongoing sulfonylurea (SU) based oral hypoglycemic agents (OHA) therapy in patients with type 2 diabetes mellitus (T2DM).MethodsA total of 19 patients with T2DM were recruited from outpatients. Vildagliptin was initiated with a dose of 100 mg per day in the patients who had inadequate glycemic control and glycemic fluctuation with ongoing SU based OHA therapy. Glycemic excursion was defined by seven-point self-monitoring blood glucose (SMBG) on three days at baseline and 12 weeks after vildagliptin-combined therapy, as well as HbA1c levels. M-value and J-index were calculated to evaluate glycemic excursion.ResultsAddition of vildagliptin to ongoing SU based OHA therapy significantly decreased HbA1c values from 8.2 ± 3.8% at baseline to 7.3 ± 0.8% at 12-week. The average of blood glucose profiles was significant improved. As a result, M-value was significantly corrected from 20.9 ± 14.4 to 12.2 ± 13.5 and J-index from 55.1 ± 25.5 to 39.1 ± 19.8.ConclusionsVildagliptin when added to ongoing SU based OHA therapy for 12 weeks significantly improved glycemic fluctuation as well as glycemic control in Japanese patients with T2DM.     

Influence of iron metabolism indices on HbA1c in non-diabetic pregnant women with and without iron-deficiency anemia: Effect of Iron supplementation

AimsCondition that influence erythrocyte turnover also affect HbA1c. Although many forms of anemia are associated with lowering of HbA1c, iron-deficiency anemia (IDA) tends to increase HbA1c. In this study, we examined the relationship between HbA1c and erythrocyte indices in non-diabetic pregnancy and assessed the effect of iron supplementation on HbA1c.Materials and Methods150 women were studied (30 non-diabetic), non-pregnant, non-anemic women in child bearing women with varying parity as controls (Gp 1); 30 non-diabetic, non-anemic pregnant women in first trimester of pregnancy (Gp 2a); 30 non-diabetic, non-anemic pregnant women in second trimester of pregnancy (Gp 2b); 30 non-diabetic, non-anemic pregnant women in third trimester of pregnancy (Gp 2c) and 30 non-diabetic pregnant women with IDA (Gp 2d). HbA1c, OGTT, erythrocyte indices and iron metabolic indices were determined in Gp 2d subjects not supplemented with iron and repeated these indices after 3 months of iron-supplementation.ResultsThe mean fasting and postprandial blood glucose levels (79.9 ± 8.0 mg/dl, 108.1 ± 14.1 mg/dl) in Gp 1 were found to be significantly lower in first trimester among Gp 2a (74.4 ± 5.3 mg/dl and 97.2 ± 11.1 mg/dl), in second trimester among Gp 2b (76.2 ± 5.2 mg/dl and 103.4 ± 7.9 mg/dl) followed by increase in IIIrd trimester among Gp 2c (82.3 ± 5.7 mg/dl and 112.5 ± 8.5 mg/dl) subjects. A significant difference in HbA1c was also observed among the groups (HbA1c 4.7 ± 0.3% in Gp 1; 4.6 ± 0.4% in Gp 2a; 4.5 ± 0.3 in Gp 2b; 4.7 ± 0.3 in Gp 2c). Among Gp 2d subjects, HbA1c was 5.2 ± 0.3% and the level decreased after iron supplementation to 5.1 ± 0.3%. Significant correlation between erythrocyte indices, iron metabolic indices and HbA1c was also observed.ConclusionWe conclude that consideration should be given for performing glucose testing in patients with IDA to ascertain the reliability of HbA1c in the diagnosis of diabetes. HbA1c concentrations in diabetic patients with IDA should be interpreted with caution.     

Serum glycated albumin predicts the progression of diabetic retinopathy—a five year retrospective longitudinal study

AimsTo assess the predictive value of glycated albumin (GA) and other risk factors on a progression of diabetic retinopathy (DR).MethodsIn this retrospective longitudinal study, we enrolled the subjects with type 2 diabetes who had undergone fundus photography twice with a 5-years gap between January 2006 and December 2012, and had been measured consecutively for hemoglobin A1c (HbA1c) and GA levels every 3 or 6 months. The subjects were divided into two groups with or without a progression of DR. The mean HbA1c and mean GA were calculated separately by the sum of all measured values divided by the numbers of values throughout the study period.ResultsOf the 359 subjects, progression group showed significantly higher diabetes duration (8.41 ± 5.72 vs. 6.46 ± 5.77, P < 0.01), baseline HbA1c (9.13 ± 2.71 vs. 8.41 ± 2.32, P < 0.05), fasting plasma glucose (8.71 ± 2.78 vs. 7.94 ± 2.63, P < 0.05), 2 h-postprandial glucose (15.12 ± 11.20 vs.13.14 ± 4.72, P < 0.05), eGFR (114.81 ± 39.15 vs. 103.23 ± 32.18, P < 0.01), mean HbA1c (8.32 ± 1.69 vs. 7.39 ± 1.35, P < 0.01) and mean GA (22.66 ± 5.92 vs. 19.83 ± 5.18, P < 0.01) than non-progression group. The frequencies of subjects with DR progression increased obviously with the increment of baseline HbA1c, mean HbA1c and mean GA according to quartile stratification of the above three glucose parameters. Multivariable binary logistic regression analysis investigated that the factors affected the DR progression were the presence of DR at baseline (OR = 0.391, P = 0.005), mean HbA1c (OR = 1.389, P = 0.021), mean GA (OR = 1.087, P = 0.039) and eGFR (OR = 1.008, P = 0.045). The optimal cut-off values of mean HbA1c and GA to predict DR progression were 7.27% and 21.85%, respectively.ConclusionsThe presence of DR at baseline, poor glycemic control, glycated albumin, and impaired renal function predicted DR progression in patients with type 2 diabetes.     

Assessing the quality of life among patients with diabetes in Austria and the correlation between glycemic control and the quality of life

BackgroundQuality of life is becoming an important health outcome and among the main goals of every healthcare intervention. This study aims to assess the reliability of the German version of the World Health Organization Quality of Life-BREF instrument (WHOQOL-BREF) among Austrian patients with diabetes and examine the correlation to glycated hemoglobin (HbA1c).MethodsThis was a cross-section study that involved 223 patients with diabetes who attended the diabetes center at Melk Hospital in Austria. The German version of the WHOQOL-BREF questionnaire was used to assess their quality of life from 2018 to 2019. The response to each question was scored from 1 to 5 (ranged from strongly disagree to strongly agree) on the Likert scale. The reliability of the WHOQOL-BREF instrument was assessed using the Cronbach’s α, and the Spearman correlation coefficient was used to examine the correlation between the quality of life and the HbA1c.ResultsThere were 208 valid WHOQOL-BREF questionnaires with a response rate of 93.7%. The overall observed Cronbach’s α for WHOQOL-BREF was 0.86. The mean ± standard deviation (SD) for the physical domain, psychological domain, social domain, and environmental domain were 61.9 ± 19.1, 71.5 ± 17.8, 71.0 ± 19.6, and 81.3 ± 11.1, respectively. There was a moderate but statistically significant negative correlation between HbA1c and the physical health domain (rs = −0.31, p < 0001). There was also a weak correlation between the HbA1c and other domains: psychological (rs = −0.23, p < 001), social relationships (rs = −0.15, p < 005) and environmental (rs = −0.23, p < 001).ConclusionThis study showed that the German form of the WHOQOL-BREF is a valid instrument to evaluate the quality of life among Austrian patients with diabetes. There was a moderate to weak negative association between WHOQOL-BREF and HbA1c.     

Reproducibility of vibration perception threshold values in children and adolescents with type 1 diabetes mellitus and associated factors

AimsTo define the reproducibility of vibration perception thresholds (VPTs) and the possible associated factors, as an early index of peripheral diabetic neuropathy (PDN) in type 1 diabetes mellitus (T1DM) children and adolescents.MethodsA single examiner studied 118 T1DM subjects (aged 13.5 ± 3.4 years) and 79 controls (aged 12.0 ± 3.07 years). Glycaemic control was assessed with HbA1c levels. VPT was measured twice on upper and lower limbs, using a Biothesiometer. Concordance between the two VPT measurements was evaluated using the Cohen's Weighted Kappa statistic (Kappa = 0.41–0.60 → moderate concordance, Kappa = 0.61–0.80 → substantial concordance).ResultsT1DM children had significantly higher VPTs than controls at all sites (p = 0.001), but with lower Kappa values (0.64–0.70). VPT values increased in parallel with HbA1c (a. < 8%, b. 8–9.5%, c. > 9.5%) and T1DM duration (a. < 5 years, b.5.1–10, c. > 10 years). However, Kappa values were lower in the groups with the poorest control (HbA1c > 9.5%) (Kappa = 0.54–0.76) or the longest T1DM duration (>10 years) (Kappa = 0.49–0.71). Although VPTs increased with stature and male gender, no effect on VPT reproducibility was observed. However, obesity was associated with lower VPT values and poorer concordance.ConclusionsThese findings suggest that the reproducibility of VPTs is lower in the high-risk patients for early subclinical PDN development, who need a regular follow-up.     

Impaired macrophage production of anti-atherosclerotic interleukin-10 induced by coronary intraplaque hemorrhage in patients with acute coronary syndrome and hyperglycemia

BackgroundCoronary intraplaque hemorrhage (IPH) accelerates atherosclerosis. Extracellular hemoglobin (Hb) released by IPH is cleared by macrophages with CD163 receptors. This process provokes secretion of the anti-atherosclerotic cytokine interleukin (IL)-10. The present study aimed to investigate the relationship between macrophage accumulation and IL-10 production provoked by IPH in plaques obtained from acute coronary syndrome (ACS) patients with hyperglycemia.MethodsIn 50 ACS patients, atherothrombotic debris was retrieved during percutaneous coronary intervention (PCI). The debris was stained with antibodies to CD163, glycophorin A (GPA, a marker of IPH) and IL-10. %CD163 was defined as the ratios of CD163-positive cells to all cells. %IL-10 and %GPA were defined as the ratio of positively stained areas per total tissue area. Based on glycosylated Hb [HbA1c (NGSP)] ≥ 6.5%, fasting blood sugar (FBS) ≥ 126 mg/dL, and insulin resistance (HOMA-IR > 2.5), patients were divided into a diabetes mellitus (DM) group (N = 18, HbA1c ≥ 6.5% or FBS ≥ 126 mg/dL), an insulin resistance (IR) group (N = 15, HOMA-IR > 2.5, HbA1c < 6.5%, and FBS < 126 mg/dL), and a normal (NR) group (N = 17).ResultsCompared to the NR group, %GPA and %CD163 were increased in the DM and IR groups. %IL-10 was similar among the three groups. However, %IL-10/%CD163 ratios were decreased in the DM (2.5 ± 0.6, P = 0.01) and IR (2.7 ± 0.8, P = 0.02) groups compared to the NR group (5.8 ± 4.7). Only in the NR group was there a significant correlation between %IL-10 and %CD163.ConclusionsImpairment of the anti-inflammatory effect provoked by IPH contributes to premature atherosclerosis even in the IR group.     

Glycaemic control is harder to achieve than blood pressure or lipid control in Irish adults with type 1 diabetes

We sought to determine the attainment of targets for glycaemic control and vascular risk reduction in an Irish cohort of T1DM adults. Of 797 patients (53% male, mean age 40.3 ± 14.8 years, HbA1c 8.5 ± 1.6% (69.6 ± 17.8 mmol mol⁻¹)), 15%, 68% and 62% achieved targets for HbA1c, blood pressure and LDL cholesterol, respectively.     

Characteristics of newly diagnosed adults with type 1 diabetes in the UK and evolution of glycaemic control,body mass index and Charlson comorbidity index over the first 5 years after diagnosis

AimsThis retrospective, longitudinal study characterised 2430 adults (mean age 40.8 ± 16.1 years) with newly diagnosed type 1 diabetes (T1D) over the first 5 years of insulin treatment.MethodsData from 1 year pre- and up to 5 years post-insulin initiation were extracted from the UK Clinical Practice Research Datalink (1990–2013). Baseline HbA_1c, BMI and Charlson comorbidity index (CCI) score were compared with data at 1, 2, 3 and 5 years.ResultsMean HbA_1c decreased significantly from baseline 95 ± 32.8 mmol/mol (10.8 ± 3.0%) to 61 ± 21.9 mmol/mol (7.7 ± 2.0%) at 1 year, remaining significantly lower at 2, 3 and 5 years (p < 0.0001). One year after initiating insulin, only 6.3% of patients had HbA_1c <48 mmol/mol (<6.5%). There was no further improvement in HbA1c after 1 year. Mean BMI increased significantly from baseline 25.3 ± 5.5 kg/m² to 27.2 ± 5.8 kg/m² at 1 year; p < 0.0001), remaining significantly higher thereafter, with over two-thirds having overweight/obesity by year 5. Mean CCI score increased significantly (1.32, baseline; 1.46, year 1; 1.75, year 5). CCI patterns were similar within BMI and HbA_1c strata.ConclusionsMore intensive support to reach and maintain glycaemic targets soon post-diagnosis, while avoiding weight gain, and prevention and optimal management of comorbidities are warranted.     

Predictors of glycemic control on insulin pump therapy in children and adolescents with type I diabetes

ObjectiveTo determine variables predictive of glycemic control in a large population of pediatric patients with type 1 diabetes on continuous subcutaneous insulin infusion (CSII).MethodsCharts of patients on CSII for ≥1 year were reviewed. “Good” control was a priori defined as HbA1c ≤9% in patients under 12 years of age, and ≤8% in patients over 12 years.ResultsNinety-three patients were identified (57 girls and 36 boys). Their mean age at pump start was 11.6 ± 3.1 years with duration of diabetes of 4.7 ± 3.1 years. Average time on pump therapy was 2.4 ± 0.8 years. HbA1C decreased from 8.7 ± 0.9% prior to pump therapy to 8.3 ± 0.6% while on CSII (p < 0.01). Despite analysis of a large number of possible predictors, only number of basal rates (4.4 versus 3.4) and younger age (10.0 years versus 13.1 years) correlated with good control.ConclusionOnly younger age and use of more basal rates were predictive of good diabetes control in children using CSII. Decisions regarding which pediatric patients are most appropriate for CSII must continue to be individualized.     

Impaired glucose metabolism is a risk factor for increased thyroid volume and nodule prevalence in a mild-to-moderate iodine deficient area

ObjectiveInsulin resistance (IR) is a key factor involved in the pathogenesis of impaired glucose metabolism. IR is associated with increased thyroid volume and nodule prevalence in patients with metabolic syndrome. Data on the association of thyroid morphology and abnormal glucose metabolism are limited. This prospective study was carried out to evaluate thyroid volume and nodule prevalence in patients with pre-diabetes and type 2 diabetes mellitus (DM) in a mild-to-moderate iodine deficient area.Materials and MethodsData were gathered on all newly diagnosed patients with pre-diabetes and type 2 diabetes mellitus between May 2008 and February 2010. 156 patients with pre-diabetes and 123 patients with type 2 DM were randomly matched for age, gender, and smoking habits with 114 subjects with normal glucose metabolism. Serum thyroid-stimulating hormone (TSH) and thyroid ultrasonography was performed in all participants.ResultsMean TSH level in the diabetes group (1.9 ± 0.9 mIU/L) was higher than in the control group (1.4 ± 0.8 mIU/L) and the pre-diabetes group (1.5 ± 0.8 mIU/L) (P < 0.0001 for both). Mean thyroid volume was higher in the pre-diabetes (18.2 ± 9.2 mL) and diabetes (20.0 ± 8.2 mL) groups than in controls (11.4 ± 3.8 mL) (P < 0.0001 for both). Percentage of patients with thyroid nodules was also higher in the pre-diabetes (51.3%) and diabetes groups (61.8%) than in controls (23.7%) (P < 0.0001 for both).ConclusionsThe results suggest that patients with impaired glucose metabolism have significantly increased thyroid volume and nodule prevalence.     

Impact of coronary artery calcification on percutaneous coronary intervention and postprocedural complications

BackgroundExcessive coronary calcification can lead to adverse outcomes after percutaneous coronary intervention (PCI). We therefore evaluated the impact of coronary calcium score (CCS) measured by multidetector computed tomography (MDCT) on immediate complications of PCI and rate of restenosis.MethodsWe performed a single-center retrospective analysis of 84 patients with coronary stenosis diagnosed by MDCT who underwent PCI. The Agatston method was used to measure total, target-vessel, and segmental (stent deployment site) CCS.ResultsIn 108 PCI procedures, 32 lesions (29.5%) were American College of Cardiology/American Heart Association type A, 60 (55.5%) were type B, and 16 (15%) were type C. ANOVA showed significantly higher segmental CCS in type C than in type A lesions (29 ± 51 vs. 214 ± 162; p = 0.03). Six patients (7.1%) had periprocedural complications and seven (8.3%) had in-stent restenosis and angina. Mean total, target-vessel, and segmental CCS was significantly higher in complicated than in successful PCI (199 ± 325 vs. 816 ± 624, p = 0.001; 92 ± 207 vs. 337 ± 157, p = 0.001; and 79 ± 158 vs. 256 ± 142, p = 0.003, respectively), but there was no significant difference in CCS between successful PCI and PCI complicated by late restenosis.ConclusionsCCS measured by MDCT has an important role in predicting early, but not late, complications from PCI.     

Can hemoglobin A1c in early pregnancy predict adverse pregnancy outcomes in diabetic patients?

ObjectiveTo examine the association of elevated early pregnancy hemoglobin A1c (HbA1c) levels with adverse pregnancy outcomes in women with preexisting diabetes mellitus.Study DesignRetrospective cohort study of 330 women with preexisting diabetes enrolled in a Diabetes in Pregnancy Program at an academic institution between 2003 and 2011 who had an early HbA1c determination. The frequencies of composite maternal adverse pregnancy outcomes (birth at < 37 weeks, preeclampsia, and medically indicated birth < 39 weeks), and composite fetal adverse pregnancy outcomes [shoulder dystocia, Apgar scores < 7 at 5 minutes, small for gestational age (SGA), large for gestational age (LGA), and stillbirth] were compared between HbA1c categories (< 6.5, 6.5–7.4, 7.5–8.4 and ≥ 8.5%).ResultsThere was no statistically significant difference between composite adverse maternal pregnancy outcomes and composite adverse fetal pregnancy outcomes as well as other individual outcomes between different HbA1c categories. Of the vaginally delivered women in our cohort, the 37 patients with HbA1c levels of ≥ 8.5% had a significantly higher frequency of fetal shoulder dystocia than the 62 with HbA1c levels of < 8.5% (24.2 vs. 1.6%, P = 0.002). Neonates of patients with HbA1c ≥ 8.5% were more likely to have low five minute Apgar scores than neonates of patients with HbA1c < 8.5%, but this was of borderline statistical significance (7.4% vs. 0.5%, P = 0.05).ConclusionIn patients with preexisting diabetes mellitus, HbA1c levels of ≥ 8.5% during early pregnancy are not useful in predicting most adverse outcomes, although there may be an increased risk for shoulder dystocia.     

Active- and placebo-controlled dose-finding study to assess the efficacy,safety, and tolerability of multiple doses of ipragliflozin in patients with type 2 diabetes mellitus

AimTo evaluate the efficacy, safety, and tolerability of multiple doses of ipragliflozin. This novel selective inhibitor of sodium glucose co-transporter 2 is in clinical development for the treatment of patients with type 2 diabetes mellitus (T2DM).MethodsIn a 12-week, multicenter, double-blind, randomized, active- and placebo-controlled dose-finding study, patients were randomized to one of four ipragliflozin treatment groups (12.5, 50, 150, and 300 mg once daily), placebo, or active control (metformin). The primary efficacy outcome was the mean change from baseline to Week 12 of glycosylated hemoglobin (HbA1c) compared with placebo.ResultsIpragliflozin showed a dose-dependent decrease in HbA1c of ? 0.49% to ? 0.81% at Week 12 compared with placebo (P < 0.001); a decrease of ? 0.72% was seen with metformin. Among the ipragliflozin groups there was also a dose-dependent reduction in body weight of up to 1.7 kg.Proportions of patients experiencing treatment-emergent adverse events were similar across all groups: ipragliflozin (45.7–58.8%), placebo (62.3%), and metformin (59.4%). No clinically relevant effects were observed for other safety measures.ConclusionsAfter 12 weeks of treatment, ipragliflozin dose-dependently decreased HbA1c, with ipragliflozin ≥ 50 mg/day in patients with T2DM; an effect comparable to metformin. No safety or tolerability concerns were identified.     

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

ObjectiveThe 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.MethodsSeventy 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.ResultsHbA1c 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).ConclusionsIn 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.