Abstract P209: Which Comes First, Type 2 Diabetes (T2DM) or Hypertension?

Abstract

Objectives: It is well demonstrated that there is a higher prevalence of hypertension (HT) in patients with type 2 diabetes (T2DM) than non-DM individuals as well as higher prevalence of DM in HT than normotensives (NT). However, it has not been clarified which of DM or HT leads to other, and what mechanisms may play a major role. Methods: In the present study, we compared neurohormonal parameters in the following 4 groups in weight loss (WL) program with a mild calorie restriction and exercise over 12 weeks; 53 obese NT without DM, 44 NT with T2DM, 68 HT without DM, and 43 HT with T2DM. HT and T2DM were all diagnosed in the last 3 months and none had medications. At entry period, the 4 groups were strictly matched in BMI and in BP. They were measured BMI, total body fat-mass, waist/hip ratio (W/H), BP, PR, HbA 1c , fasting glucose, insulin (HOMA-IR), norepinephrine (NE) and leptin (LEP) at entry, 4 and 12 weeks. Results: At entry, fat-mass was greater in subjects with T2DM than non-DM in both NT and HT and HT had slightly greater fat-mass than NT, although BMI were strictly matched in the 4 study groups. HbA 1c in T2DM was greater than non-DM, and slightly greater in HT than NT. Fasting insulin was greater in HT and T2DM than NT or non-DM, and HOMA-IR was slightly greater in HT than NT and significantly greater in T2DM than non-DM. LEP was similar between NT and HT, but it was greater in T2DM than non-DM. (HbA 1c , HT with T2DM>NT with T2DM>>HT without DM>NT without DM; Insulin, HT with T2DM>NT with T2DM>>HT without DM>NT without DM; NE, HT with T2DM>>HT without DM≥NT with T2DM>>NT without DM; LEP, HT with T2DM≈NT with T2DM>>HT without DM>NT without DM). WL over 12 wks in HT and T2DM were smaller than those in NT or non-DM. At 12 weeks, in HT groups regardless of T2DM, percent (%) decreases in plasma NE and BP, and reductions in HbA 1c were smaller than those in NT groups, although reductions in fat-mass and leptin were similar. In T2DM groups regardless of BP levels at entry, reductions in BMI, BP, HbA 1c , HOMA-IR and NE were smaller than those in non-DM group. In the 4 groups, reductions in plasma NE was observed at first followed by reductions in HOMA-IR, HbA 1c, BMI and BP over 12 weeks. Conclusions: These findings demonstrate that insulin resistance (IR) may play an important role on the onset of T2DM and high plasma NE appears to cause HT. HT had resistance to normalized high plasma NE and %reductions in NE, and T2DM had resistance to normalize IR and sympathetic overactivity. We previously reported that high plasma NE could predict future weight gain and BP elevation, and high NE preceded IR in non-obese subjects. Taken together, sympathetic overactivity observed in high NE may cause obesity and HT, and then IR seems to start with weight gain leading T2DM, suggesting that HT may lead to T2DM with this mechanisms.