Journal of Investigative Medicine

The aim of the study was to identify factors associated with progressive beta-cell failure in a cohort of nonselected subjects with type 2 diabetes.

Two hundred twenty-four medical records were evaluated. Progressive beta-cell failure was defined as the following: glycated hemoglobin is higher than 7.5% despite combined drug therapy and appropriate diet (ie, isocaloric or hypocaloric diet depending on body weight) and absence of any illness causing acute hyperglycemia. The following factors were considered as possible predictors: diabetes-related symptoms, fasting plasma glucose at the onset of disease, family history of type 2 diabetes, number of visits per year, and residency. Further potential predictors were disease duration, age, body mass index, estimated glomerular filtration rate, and hypertension and/or hyperlipidemia at the enrollment in the study.

The prevalence of beta-cell failure was 41%. Independent predictors of failure were longer disease duration (hazard ratio [HR] for each year of diabetes, 1.03; confidence intervals (CIs), 1.01–1.05; P = 0.03), history of hypertension (HR, 1.90; CIs, 1.73–2.89; P = 0.04), hyperlipidemia (HR, 1.65; CIs, 1.06–2.58; P = 0.03), residence in suburb (HR, 1.78; CIs, 1.06–3.01; P = 0.03), and presence of symptoms at the onset of disease (HR, 2.47; CIs, 1.51–4.03; P = 0.0001).

Patients with long disease duration, hypertension, and hyperlipidemia who are residents in suburbs and had diabetes-related symptoms at diagnosis might deserve intensive treatment to obtain adequate and stable glycemic control.

The infusion of low-dose dopamine is normally associated with an increase in creatinine clearance, thereby allowing one to assess renal functional reserve. Increased renal blood flow is also associated with a reduction in erythropoietin (EPO) levels.

We evaluated the use of dopamine infusion in subjects with IgA nephropathy to determine if these functional changes correlate with risk factors for progression and compared this to the renal biopsy findings.

Changes in creatinine clearance and EPO levels were determined in 46 non-nephrotic IgA patients with relative preserved renal function after the infusion of low dose dopamine. Control subjects (n = 15) were evaluated using similar protocols.

Subjects with IgA nephropathy could be separated into those who showed a fall in EPO levels (n = 24) and those who showed no change or a rise in EPO levels (n = 22). Subjects showing the expected fall in EPO demonstrated a higher increase in creatinine clearance, similar to that observed in control subjects. Most importantly, subjects who showed a fall in EPO had less proteinuria, less N-acetyl-β-D-glucosaminidase excretion, lower serum uric acid, blood pressure, and less features of metabolic syndrome despite similar inflammation and fibrosis on biopsy as compared to the others.

A decrease in EPO in response to dopamine is associated with a clinical phenotype that is less likely to develop progressive renal disease. These studies suggest that a fall in EPO in response to dopamine likely reflects preserved tubulointerstitial function that cannot be assessed by renal biopsy alone.

Primary aldosteronism (PA) is one of the major etiologies for secondary hypertension featuring more prominent left ventricular hypertrophy. The purpose of the study was to investigate the predictive factors of left ventricular mass index (LVMI) regression in patients with PA after adrenalectomy.

We prospectively analyzed 30 patients with aldosterone-producing adenoma (APA) who received adrenalectomy from October 2006 to September 2008. Echocardiography was performed preoperation and 1 year after operation.

Thirty patients with aldosterone-producing adenoma undergoing adrenalectomy were enrolled. In a 1-year follow-up, LVMI decreased significantly by an average of 18.6%. Net LVMI decrease (ΔLVMI) was associated with preoperative LVMI, preoperative serum potassium level, baseline systolic blood pressure (SBP), baseline diastolic blood pressure, net SBP decrease (ΔSBP), net diastolic blood pressure decrease, preoperative/postoperative change of log-transformed plasma aldosterone concentration, preoperative/postoperative change of log-transformed plasma renin activity, and preoperative/postoperative change of serum potassium level (Δserum potassium level). In a multiple regression analysis, preoperative LVMI (β = −0.287, P = 0.049), ΔSBP (β = 0.518, P = 0.01), and Δserum potassium level (β = −20.471, P = 0.014) were significantly correlated with ΔLVMI.

The LVMI in patients with PA regressed significantly after adrenalectomy. Preoperative LVMI, ΔSBP, and Δserum potassium levels are independent factors associated with the degree of LVMI regression.

The aim of the study was to evaluate the predictive value of HbA_1c for risk of overall mortality or a composite endpoint of death and nonfatal events.

Logistic regression retrospectively assessed the longitudinal association of measured HbA_1c with outcome in 746 middle-aged adults, recruited from a tertiary health center and stratified to absence or presence of type 2 diabetes, using the recent American Diabetes Association criteria.

A total of 70 deaths and additional incident nonfatal events in 82 cases were recorded at a median of 3.1-year follow-up. Multivariable linear regression revealed among nondiabetic individuals HbA_1c to be significantly associated—independent of fasted glucose—inversely with triglycerides and high-density lipoprotein cholesterol, distinct from the diabetic sample. Sex and diabetes status differed in baseline HbA_1c values with respect to the development of outcome. Nondiabetic men who subsequently died exhibited significantly lower HbA_1c, as did men and women with incident coronary heart disease. Similar difference was observed for incident hypothyroidism and nondiabetic subjects developing malignancy. In logistic regression analysis, adjusted for sex, age, and fasting glucose, each 0.7% (SD, 1) decrement of baseline HbA_1c predicted the composite endpoint in the nondiabetic sample (risk estimates, 1.49%; 95% confidence interval, 1.07–2.04), but not in the diabetic sample, whereas overall mortality in the whole sample was increased (risk estimates, 1.51%; 95% confidence interval, 1.05–2.17).

Inverse association of HbA_1c with adverse outcomes in men and nondiabetic people indicates the involvement of HbA_1c levels in autoimmune activation. The weaker inverse association with prevalent diabetes and in women is consistent with the operation of more pronounced confounding autoimmune processes.