Protamine as a barrier against the angiogenic effect of insulin: a possible role of apelin.

Insulin is proved to have angiogenic ability thereby may worsen the diabetic retinopathy (DR) progression. Insulin also triggers the expression of endogenous angiogenic peptide, apelin. Since protamine was introduced as an inhibitor of the apelin receptor, we hypothesized that use of protaminated insulin instead of non-protaminated insulin can decrease the negative role of insulin in progression of DR. Firstly, the incidence of DR was compared among three diabetic patient groups: an oral medication, non-protaminated insulin, and protaminated insulin (PIns). Proliferation and migration rate of HUVECs was measured after insulin, apelin, and protamine exposure. In clinical study, the chance of developing DR was 8.5 and 4.1 times higher in insulin group and PIns groups compared with oral group respectively. Insulin group had a chance of 9.5-folds of non-proliferative DR compared to oral group. However, the difference of non-proliferative DR between PIns and oral group wasn't significant. In-vitro tests showed that concomitant use of insulin and apelin increases viability and migratory potential of HUVECs. However, protamine could reverse this effect. Protamine present in some insulins might show a promising protective role against diabetic retinopathy. Thus, protaminated insulins may be preferable in the treatment of diabetes.

Prevalence and 5-year incidence rate of dyslipidemia and its association with other coronary artery disease risk factors in Iran: Results of the Kerman coronary artery disease risk factors study (Phase 2).

BACKGROUND: Dyslipidemia (DL) is an important risk factor of coronary artery disease (CAD). We evaluated DL prevalence and its 5-year incidence rate in southeastern Iran, to assess the severity and growth rate of this CAD risk factor in the region. MATERIALS AND METHODS: This study was a part of the Kerman CAD Risk Factors Study Phase 2 (2014-2018) among 9996 individuals aged 15-80 years, from whom 2820 individuals had also participated in Phase 1 (2009-2011). In mg/dl, cholesterol ≥240 and/or low-density lipoprotein cholesterol ≥160 and/or high-density lipoprotein cholesterol <40 for men and <50 for women and/or triglyceride >200 were defined as DL. RESULTS: The lipid profile of 9911 persons was analyzed. Overall 19.6% had borderline cholesterol and 6.4% suffered from hypercholesterolemia. 56.6% of the population (62.5% of females vs. 48.5% of males) suffer from DL, from whom 73.4% were undiagnosed. Female gender, advanced age, obesity, hypertension, diabetes, anxiety, and depression predicted DL in the study population. The prevalence of DL was significantly lower in Phase 2 (56.6%) compared to Phase 1 (81.4%). The prevalence of undiagnosed DL (UDL) and diagnosed DL (DDL) was 40.7% and 16.2%, respectively. The 5-year incidence rate of DL was 2.58 persons/100 person-years (3.24 in females vs. 2.20 in males). CONCLUSION: Although there were promising signs of a reduction in DL and increase in DDL in the last 5 years, a high percentage of the population have DL yet, from whom mostly are undiagnosed. DL was significantly associated with other CAD risk factors. Therefore, the health-care management system should improve its strategies to reduce the health burden of DL.