Short term optimization of glycaemic control using insulin improves sympatho-vagal tone activities in patients with type 2 diabetes.

INTRODUCTION: Diabetic cardiac autonomic neuropathy (CAN) is potentially life threatening and its severity might further be aggravated by poor glycaemic control. A decrease in Heart rate variability (HRV) is the earliest finding of CAN even at the sub clinical stage. While intensive glycaemic control prevents the development of CAN in patients with type 1 diabetes, it is not known whether the intensification of glycaemic control using insulin would improve cardiovascular autonomic functions in type 2 diabetes patients. This study aimed to determine the short term effects of optimizing glycaemic control using insulin on the HRV in type 2 diabetes patients. METHODS: We conducted a single arm open label clinical trial. Participants were poorly controlled non-insulin treated type 2 diabetes mellitus patients (HbA1c ≥ 7%). The intervention lasted 60 days and consisted in the intensification of glycaemic control through the initiation of a basal plus insulin regimen with titration of insulin to protocol defined glycaemic targets which were; fasting glycaemia: 0.70-1.30 g/L and post prandial glycaemia <1.80 g/L. Long term HRV measurement was done using a 24-h ambulatory electrocardiographic (ECG) recording on day 0 and day 60. Wilcoxon signed rank test was used to compare differences in HRV parameters before and after the intervention. RESULTS: A total of 29 (14 males and 15 females) consenting type 2 diabetes mellitus patients without clinical signs of CAN were enrolled and allocated to intervention (14 males and 15 females). The median age was 52 [43-59] years, and duration of diabetes 3.0 [0.6-6.7] years. The intervention induced a reduction in HbA1c from 10.1 [9.1-11.9]% to 6.7 [5.9-6.9]% (p < 0.001) without severe hypoglycaemic events. Concerning HRV parameters, there was a significant improvement in markers of the parasympathetic tone (PNN50: 5.7 [3.6-10.3]% to 8.1 [3.1-16.9]%, p = 0.008) and sympathetic tone (SDNN: 102.01 [90.45-111.05] ms to 122.40 [91.70-135.95] ms, p = 0.01). CONCLUSION: The optimization of glycaemic control using a basal plus insulin regimen while inducing a significant reduction in glycated hemoglobin, significantly improves 24-h ambulatory ECG derived sympathetic and parasympathetic activities. This suggests that tight glycaemic control using insulin may revert cardiac autonomic neuropathy in type 2 diabetes mellitus patients.

Exercise-induced albuminuria and circadian blood pressure abnormalities in type 2 diabetes.

AIM: To investigate the relationship between circadian variations in blood pressure (BP) and albuminuria at rest, and during exercise in non-hypertensive type 2 diabetes (T2D) patients. METHODS: We conducted a cross-sectional study in well controlled T2D patients, non-hypertensive, without clinical proteinuria and normal creatinine clearance. In each participant, we recorded the BP using ambulatory blood pressure monitoring (ABPM) for 24-h, and albuminuria at rest and after a standardized treadmill exercise. RESULTS: We enrolled 27 type 2 patients with a median age of 52; and a mean duration of diabetes and HbA1c of 3.6 ± 0.8 years and 6.3% ± 0.5% respectively. Using a 24-h ABPM, we recorded a mean diurnal systolic blood pressure (SBP) of 128 ± 17 mmHg vs nocturnal of 123 ± 19 mmHg (P = 0.004), and mean diurnal diastolic blood pressure (DBP) of 83 ± 11 mmHg vs nocturnal 78 ± 14 mmHg (P = 0.002). There was a significant difference between albuminuria at rest [median = 23 mg, interquartile range (IQR) = 10-51] and after exercise (median = 35 mg, IQR = 23-80, P < 0.001). Patients with exercise induced albuminuria had an increase in nocturnal BP values on all three components (128 mmHg vs 110 mmHg, P = 0.03 for SBP; 83 mmHg vs 66 mmHg, P = 0.04; 106 vs 83, P = 0.02 for mean arterial pressure), as well as albuminuric patients at rest. Moreover, exercise induced albuminuria detect a less increase in nocturnal DBP (83 vs 86, P = 0.03) than resting albuminuria. CONCLUSION: Exercise induced albuminuria is associated with an increase in nocturnal BP values in T2D patients.

An assessment of discriminatory power of office blood pressure measurements in predicting optimal ambulatory blood pressure control in people with type 2 diabetes.

INTRODUCTION: Ambulatory blood pressure (BP) measurements (ABPM) predict health outcomes better than office BP, and are recommended for assessing BP control, particularly in high-risk patients. We assessed the performance of office BP in predicting optimal ambulatory BP control in sub-Saharan Africans with type 2 diabetes (T2DM). METHODS: Participants were a random sample of 51 T2DM patients (25 men) drug-treated for hypertension, receiving care in a referral diabetes clinic in Yaounde, Cameroon. A quality control group included 46 non-diabetic individuals with hypertension. Targets for BP control were systolic (and diastolic) BP. RESULTS: Mean age of diabetic participants was 60 years (standard deviation: 10) and median duration of diabetes was 6 years (min-max: 0-29). Correlation coefficients between each office-based variable and the 24-h ABPM equivalent (diabetic vs. non-diabetic participants) were 0.571 and 0.601 for systolic (SBP), 0.520 and 0.539 for diastolic (DBP), 0.631 and 0.549 for pulse pressure (PP), and 0.522 and 0.583 for mean arterial pressure (MAP). The c-statistic for the prediction of optimal ambulatory control from office-BP in diabetic participants was 0.717 for SBP, 0.494 for DBP, 0.712 for PP, 0.582 for MAP, and 0.721 for either SBP + DBP or PP + MAP. Equivalents in diabetes-free participants were 0.805, 0.763, 0.695, 0.801 and 0.813. CONCLUSION: Office DBP was ineffective in discriminating optimal ambulatory BP control in diabetic patients, and did not improve predictions based on office SBP alone. Targeting ABPM to those T2DM patients who are already at optimal office-based SBP would likely be more cost effective in this setting.

Acute phase ketosis-prone atypical diabetes is associated with a pro-inflammatory profile: a case-control study in a sub-Saharan African population.

BACKGROUND: It is unknown whether inflammation plays a role in metabolic dysfunction on ketosis-prone diabetes (KPD). We aimed to assess the inflammatory profile in sub-Saharan African patients with KPD during the acute ketotic phase as well as during non-ketotic hyperglycemic crises. METHODS: We studied 72 patients with non-autoimmune diabetes: 23 with type 2 diabetes mellitus (T2D), and 49 with KPD, all admitted in hyperglycemic crisis (plasma glucose ≥250 mg/dl). The T2D and KPD groups were matched by sex, age, and Body Mass Index. KPD was sub-classified into new-onset ketotic phase (n = 34) or non-ketotic phase (n = 15). We measured TNF-α, MCP-1, MIP1-α, IL-8, MIP1-ß, and VEGF in the serum of all participants. RESULTS: TNF-α and IL-8 were higher in participants with KPD compared to those with T2D (p = 0.02 TNF-α; p = 0.03 IL-8). TNF-α and IL-8 were also higher in the ketotic phase KPD group compared to the T2D group (p = 0.03 TNF-α; p < 0.001 IL-8) while MIP1-α was lower in people with ketotic phase KPD compared to their T2D counterparts (p = 0.03). MIP1-α was lower in the ketotic phase KPD group compared to the non-ketotic phase KPD group (p = 0.04). MCP-1 was lower in non-ketotic phase KPD compared to T2D (p = 0.04), and IL-8 was higher in non-ketotic phase KPD compared to T2D (p = 0.02). CONCLUSIONS: Participants with KPD had elevated pro-inflammatory cytokines compared to their T2D counterparts. Ketotic phase KPD is associated with a different pro-inflammatory profile compared to non-ketotic phase KPD, and the inflammatory profile appears to be comparable between non-ketotic phase KPD and T2D patients.