Cardiovascular autonomic dysfunction in type 2 diabetes mellitus and essential hypertension in a South Indian population.

Diabetes mellitus (DM) and hypertension (HTN) are risk factors for cardiovascular disease. There has been an alarming rise in their incidence especially in developing countries like India. The global prevalence of diabetes cases is 285 million, of which India harbors 50.8 million cases, whereas the prevalence of HTN globally is 972 million, and India accounts for 65.5 million cases. The coexistence of type 2 diabetes mellitus (T2DM) and essential HTN is common. Previous studies have demonstrated that both diabetes and HTN impair cardiovascular autonomic function. 1 However, the combined effects of diabetes and HTN on cardiovascular autonomic control have not been fully understood. We hypothesize that the association of these 2 diseases might have an additive or synergistic role in affecting the cardiovascular system and in hastening autonomic dysfunction. Thus, the objective of this study was to assess the presence of cardiovascular autonomic dysfunction in T2DM and HTN patients, and those affected with both diabetes and HTN. A case-control study was conducted after approval from the Institutional Ethics Committee and obtaining written consent from all participants from February 2007 to June 2009 on 63 volunteers in the age group of 37-65 years at Osmania Medical College, Hyderabad, South-India. The inclusion criteria were normotension, HTN and T2DM, and the subjects were divided into 4 groups: non-diabetic normotensives (group I, control group), non-diabetic hypertensives (group II), diabetic normotensives (group III), and diabetic hypertensives (group IV). Plasma glucose levels were assessed by the glucose oxidase method and sphygmomanometer (Diamond, Pune, India) was used to measure left arm arterial blood pressure (BP). Lead II ECG was recorded using an automated ECG machine (Cardiart 408, BPL Ltd., Bengaluru, India) for calculating heart rate (HR). Fasting plasma glucose level of ≤110 mg/dL without the previous diagnosis of DM were labeled non-diabetics, whereas levels >110 mg/dL or within normal range but with a previous history of diabetes and treatment were labeled diabetics. A systolic BP (SBP) of ≤140 mm Hg and diastolic BP (DBP) of ≤90 mm Hg without the previous diagnosis of HTN were labeled normotensives, whereas SBP >140 and/or DBP >90 mm Hg, or within normal range but with previous history of HTN or treatment were labeled hypertensives. The exclusion criteria were (a) type 1 diabetes and secondary causes of diabetes, (b) secondary causes of HTN, (c) gross nutritional deficiency, (d) exposure to alcohol, heavy metals, neurotoxic drugs, and drugs affecting the autonomic function, (e) established diseases like ischemic heart disease, stroke, nephropathy, and (f ) symptoms related to autonomic neuropathy, such as, postural hypotension, localized sweating, urinary incontinence, urinary retention, constipation, and diarrhea. Autonomic function tests included orthostatic change in HR, orthostatic change in BP, HR response to deep breathing, Valsalva maneuver, sustained handgrip test, and cold pressor test. Baseline HR and BP were recorded in a lying down position, after which the subject was made to stand (orthostatic change). A rapid increase in HR maximal at around the fifteenth beat after standing, with a subsequent relative bradycardia, minimal at around the thirtieth beat occurs through a vagally mediated response. The HR at the fifteenth and thirtieth beat is estimated, and a 30/15 ratio computed. A ratio of 30 mm Hg and DBP for >10 mm Hg is considered abnormal. Subjects were asked to breathe deeply at a rate of 6 breaths per minute with equal time for inspiration and expiration (5 seconds each). Autonomic insufficiency was considered present when the decrease in HR was <10 beats/minute. The Valsalva maneuver was performed by asking subjects to blow into a mercury manometer maintaining the pressure at around 40 mm Hg for 30 seconds. The reflex response to the Valsalva maneuver includes tachycardia and peripheral vasoconstriction during strain, followed by bradycardia after release. The Valsalva ratio is calculated by dividing the maximum HR during the maneuver with the minimum HR after the maneuver. If the ratio is <1.1, it is abnormal. Sustained handgrip test was performed by asking the subjects to compress the hand dynamometer (Jetter & Scheerer, Tuttlingen, Germany) with maximum effort using the dominant