Circulating Angiogenic Growth Factors in Diabetes Patients with Peripheral Arterial Disease and Exertional Leg Pain in Ghana.

OBJECTIVE: Peripheral arterial disease (PAD) is a common complication of diabetes, associated with impairment in angiogenesis. Angiogenesis is regulated by angiogenic growth factors such as angiopoietin 1 (Ang-1), Ang-2, and vascular endothelial growth factor (VEGF). We studied the association between angiogenic growth factors versus PAD and exertional leg symptoms in diabetes patients in Ghana. METHOD: In this cross-sectional study, ankle-brachial index was measured with oscillometrically and exertional leg symptoms were screened with Edinburgh claudication questionnaire in 140 diabetes patients and 110 nondiabetes individuals. Circulating levels of Ang-1, Ang-2, and VEGF were measured with immunosorbent assay. RESULTS: The prevalence of PAD and exertional leg pain was 16.8% and 24.8%, respectively. Compared to non-PAD participants, PAD patients had higher VEGF levels [85.8 (37.5-154.5) versus 57.7 (16.6-161.1) p = 0.032] and lower Ang-1 levels [31.3 (24.8-42.6) versus 40.9 (28.2-62.1), p = 0.017]. In multivariable logistic regression, patients with exertional leg pain had increased the odds of plasma Ang-2 levels [OR (95% CI): 2.08 (1.08-6.41), p = 0.036]. CONCLUSION: Diabetes patients with PAD and exertional leg pain have imbalance in angiogenic growth factors, indicating impaired angiogenesis. In patients with exertional leg pains, Ang-2 may be an important biomarker.

Circulating angiogenic factors in diabetes patients in a tertiary hospital in Ghana.

BACKGROUND: Impaired angiogenesis is amongst the underlining mechanisms of organ damage in diabetes and hypertensive patients. In diabetes and hypertensive patients without proteinuria and overt CVDs, we studied the levels of angiogenic growth factors, angiopoietin (Ang)-1, Ang-2 and vascular endothelial growth factor (VEGF), and the relationship between these angiogenic growth factors and renal function, measured as estimated glomerular filtration rate (eGFR). METHOD: In a case control design, 107 type 2 diabetes (T2DM) patients and 93 non-diabetes controls were recruited into the study. Levels of plasma glucose, lipids, creatinine and angiogenic growth factors; Ang-1, Ang-2 and VEGF measured from fasting blood samples. Estimated glomerular filtration rate (eGFR) was computed using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) algorithm and eGFR < 60 ml/min/1.73 m2 was considered to be low. Multivariable logistic regression was used to assess the odds of change in angiogenic growth factors among patients with diabetes and hypertension, and patients with low eGFR, compared to those without these conditions. RESULTS: In a total of 200 participants with 49 % females and mean age of 54.1 ± 10.2 years, 22.7 % of T2DM patients and 13.3 % of non-diabetes participant had low eGFR. The levels of Ang-1 and Ang-2 were highest in hypertensive T2DM patients, followed by patients with either T2DM or hypertension alone, with the controls having the lowest levels. The odds of change in circulating Ang-2 levels increased in patients with both diabetes and hypertension [11.76 (7.97-16.63), p < 0.01] compared to patients with either diabetes [5.45 (3.31-9.71), p = 0.02] or hypertension [5.45 (3.31-9.71), p = 0.02] alone. Compared to those with normal eGFR, the odds of change in serum Ang-2 levels were increased in patients with low eGFR in both the crude [1.26 (1.08-2.110), p = 0.023] and adjusted [1.14 (1.03-2.34), p = 0.043] regression models. CONCLUSION: In our study population, having diabetes and hypertension increased the levels of Ang-1 and Ang-2. Also, low eGFR status was associated with increased levels of Ang-2 after adjustment for other risk factors.

Arterial Stiffness in Nonhypertensive Type 2 Diabetes Patients in Ghana.

Background. Increased arterial stiffness is an independent cardiovascular risk factor in diabetes patients and general population. However, the contribution of diabetes to arterial stiffness is often masked by coexistent obesity and hypertension. In this study, we assessed arterial stiffness in nonhypertensive, nonobese type 2 diabetes (T2DM) patients in Ghana. Methods. In case-control design, 166 nonhypertensive, nonobese participants, comprising 96 T2DM patients and 70 nondiabetes controls, were recruited. Peripheral and central blood pressure (BP) indices were measured, and arterial stiffness was assessed as aortic pulse wave velocity (PWVao), augmentation index (AIx), cardioankle vascular index (CAVI), and heart-ankle pulse wave velocity (haPWV). Results. With similar peripheral and central BP indices, T2DM patients had higher PWVao (8.3 ± 1 versus 7.8 ± 1.3, p = 0.044) and CAVI (7.9 ± 1.2 versus 6.9 ± 0.7, p = 0.021) than nondiabetic control. AIx and haPWV were similar between T2DM and nondiabetic controls. Multiple regression models showed that, in the entire study participants, the major determinants of PWVao were diabetes status, age, gender, systolic BP, and previous smoking status (ß = 0.22, 0.36, 0.48, 0.21, and 0.25, resp.; all p < 0.05); the determinants of CAVI were diabetes status, age, BMI, heart rate, HbA1c, total cholesterol, HDL cholesterol, and previous smoking status (ß = 0.21, 0.38, 0.2, 0.18, 0.24. 0.2, -0.19, and 0.2, resp.; all p < 0.05). Conclusion. Our findings suggest that nonhypertensive, nonobese T2DM patients have increased arterial stiffness without appreciable increase in peripheral and central pressure indices.

Arterial stiffness in hypertensive and type 2 diabetes patients in Ghana: comparison of the cardio-ankle vascular index and central aortic techniques.

BACKGROUND: Diabetes and hypertension increase arterial stiffness and cardiovascular events in all societies studied so far; sub-Saharan African studies are sparse. We investigated factors affecting arterial function in Ghanaians with diabetes, hypertension, both or neither. METHOD: Testing the hypothesis that arterial stiffness would progressively increase from controls to multiply affected patients, 270 participants were stratified into those with diabetes or hypertension only, with both, or without either. Cardio-ankle vascular index (CAVI), heart-ankle pulse wave velocity (haPWV), aortic PWV (PWVao) by Arteriograph, aortic and brachial blood pressures (BP), were measured. RESULTS: In patients with both diabetes and hypertension compared with either alone, values were higher of CAVI (mean ± SD, 8.3 ± 1.2 vs 7.5 ± 1.1 and 7.4 ± 1.1 units; p < 0.05), PWVao (9.1 ± 1.4 vs 8.7 ± 1.9 and 8.1 ± 0.9 m/s; p < 0.05) and haPWV (8.5 ± 1 vs 7.9 ± 1 and 7.2 ± 0.7 m/s; p < 0.05) respectively. In multivariate analysis, age, having diabetes or hypertension and BMI were independently associated with CAVI in all participants (ß = 0.49, 0.2, 0.17 and -0.2 units; p < 0.01, respectively). Independent determinants of PWVao were heart rate, systolic BP and age (ß = 0.42, 0.27 and 0.22; p < 0.01), and for haPWV were systolic BP, age, BMI, diabetes and hypertension status (ß = 0.46, 0.32, -0.2, 0.2 and 0.11; p < 0.01). CONCLUSION: In this sub-Saharan setting with lesser atherosclerosis than the western world, arterial stiffness is significantly greater in patients with coexistent diabetes and hypertension but did not differ between those with either diabetes or hypertension only. Simple, reproducibly measured PWV/CAVI may offer effective and efficient targets for intervention.

Body composition and ankle-brachial index in Ghanaians with asymptomatic peripheral arterial disease in a tertiary hospital.

BACKGROUND: Ankle-brachial index (ABI) and indices of obesity are both use to indicate cardiovascular risk. However, association between body composition indices and ABI, a measure of peripheral arterial disease, is inconsistent in various study reports. In this study, we investigated the relationship between ABI and general and central indices of obesity in Ghanaians without history of cardiovascular diseases. METHOD: In a case-control design, ABI was measured in a total of 623 subjects and categorised into PAD (ABI ≤ 0.9, n = 261) and non-PAD (ABI > 0.9, n = 362) groups. Anthropometric indices, BMI, waist circumference (WC), waist-hip ratio (WHR) and waist-height ratio (WHtR) were also measured. RESULTS: PAD subjects had higher mean BMI (29.8 ± 8.7 vs. 26.5 ± 7.6 kg/m(2), p = 0.043) and waist circumference (95 ± 15 vs. 92 ± 24 cm, p = 0.034) than non-PAD subjects. In multivariable logistic regression models, having BMI ≥ 30 kg/m(2) increased the odds of both unilateral [OR (95 % CI): 2 (1.14-3.51), p < 0.01] and overall PAD [2 (1.22-3.27), p < 0.01]. CONCLUSION: In indigenous Ghanaians in our study, PAD participants had higher BMI and waist circumference than non-PAD participants. Also, halving BMI ≥ 30 kg/m(2) was associated with twofold increase in the odds of PAD.

Peripheral sensory neuropathy in type 2 diabetes patients: A case control study in Accra, Ghana.

OBJECTIVE: Peripheral sensory neuropathy (PSN) is a common cause of ulceration and amputation in diabetes (DM) patients. The prevalence of PSN in DM patients is largely undetermined in sub-Saharan African population. We studied the burden of PSN in DM patients using a validated questionnaire and quantitative sensory test. METHODS: In a case-control design, PSN was measured in 491 DM patients and 330 non-DM controls using Michigan neuropathy screening instrument (MNSI) and vibration perception threshold (VPT). PSN was defined as MNSI symptom score ≥7, MNSI examination score ≥2 or VPT ≥25V. RESULTS: The prevalence of PSN screened by MNSI symptom score, MNSI examination score and VPT was 7.1%, 51.5% and 24.5% in DM patients; and 1.5%, 24.5% and 8.5% in non-DM participants respectively. The major determinants of PSN screened by MNSI examination score were diabetes status [OR (95% CI): 4.31 (2.94-6.31), p < 0.001], age [1.03 (1.01-1.05), p < 0.001], previous [4.55 (2.11-9.82), p < 0.001] and current [8.16 (3.77-17.68), p < 0.001] smoking status. The major determinants of PSN screened by VPT were diabetes status [1.04 (1.02-1.06), p < 0.001], age [1.02 (1.01-1.03), p = 0.047], heart rate [1.78 (1.08-2.92), p = 0.023], second-hand smoking [3.66 (2.26-5.95), p < 0.001] and body height [3.28 (1.65-8.42), p = 0.015]. CONCLUSION: Our study has shown high burden of PSN in DM patients in Ghana using simple, accurate, and non-invasive screening tools like MNSI and neurothesiometer.

Short-term administration of an aqueous extract of kalanchoe integra var. crenata (Andr.) Cuf leaves produces no major organ damage in Sprague-Dawley rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Kalanchoe intergra (Ki) leaf extract is an orally administered multipurpose plant medicine in Ghana and other parts of the world for the treatment of ulcers, pain and adenoma of the prostate gland. There is paucity of information concerning its short-term usage. The present study is aimed at conducting histopathological and biochemical studies in a 14-day sub-acute toxicity studies using female Sprague-Dawley rats. MATERIALS AND METHODS: Crude extract of Ki leaves was prepared and freeze-dried. A 14-day sub-acute toxicity studies was conducted using 2 week old nulliparous and non-pregnant female Sprague-Dawley rats (120-150g). Reconstituted Ki was administered at a dosage of 900mgkg(-1) (high dose), 300mgkg(-1) with a control group receiving an equivalent volume of distilled water (as vehicle) by gastric lavage. Histopathological studies of major organs and blood chemistry analysis were performed on blood obtained via cardiac puncture into EDTA tubes after euthanisation. RESULTS: There was a significant decrease in urea (p<0.016) and creatinine levels (p<0.001) in both the high and low dose groups. There was an increase in ALP levels (P=0.01) in both the high and low dose groups. ALT and AST rather decreased significantly in both the high and low dose groups (p<0.0001). Histopathological results did not show any abnormalities in all the H&E stained paraffin sections. Thus the photomicrographs of the liver, kidney and heart were within histopathological limits. CONCLUSION: Ki leaf extract is non-toxic when administered by the oral route over a time period of 14 days at the above doses.

Brain regulation of appetite and satiety.

Interest in the control of feeding has increased as a result of the obesity epidemic and rising incidence of metabolic diseases. The brain detects alterations in energy stores and triggers metabolic and behavioral responses designed to maintain energy balance. Energy homeostasis is controlled mainly by neuronal circuits in the hypothalamus and brainstem, whereas reward and motivation aspects of eating behavior are controlled by neurons in limbic regions and the cerebral cortex. This article provides an integrated perspective on how metabolic signals emanating from the gastrointestinal tract, adipose tissue, and other peripheral organs target the brain to regulate feeding, energy expenditure, and hormones. The pathogenesis and treatment of obesity and abnormalities of glucose and lipid metabolism are discussed.

Inhibition of ADRP prevents diet-induced insulin resistance.

Diets with high fat content induce steatosis, insulin resistance, and type 2 diabetes. The lipid droplet protein adipose differentiation-related protein (ADRP) mediates hepatic steatosis, but whether this affects insulin action in the liver or peripheral organs in diet-induced obesity is uncertain. We fed C57BL/6J mice a high-fat diet and simultaneously treated them with an antisense oligonucleotide (ASO) against ADRP for 4 wk. Glucose homeostasis was assessed with clamp and tracer techniques. ADRP ASO decreased the levels of triglycerides and diacylglycerol in the liver, but fatty acids, long-chain fatty acyl CoAs, ceramides, and cholesterol were unchanged. Insulin action in the liver was enhanced after ADRP ASO treatment, whereas muscle and adipose tissue were not affected. ADRP ASO increased the phosphorylation of insulin receptor substrate (IRS)1, IRS2, and Akt, and decreased gluconeogenic enzymes and PKCepsilon, consistent with its insulin-sensitizing action. These results demonstrate an important role for ADRP in the pathogenesis of diet-induced insulin resistance.

Does losartan prevent cerebral edema? A preliminary study using a vascular compartment model.

BACKGROUND: The purpose of this study was to ascertain the effect of Losartan, a non-peptide angiotensin II receptor antagonist used for the treatment of hypertension, on the movement of proteins and fluids across the vascular compartment in ischemic cat brains. MATERIAL/METHODS: The experiments were carried out on anesthetized cats under artificial ventilation and autohemoperfusion of the brain with a stable volume of blood with the help of a resistograph. Cerebral ischemia was induced by a 15-minute arrest of the autohemoperfusion pump, tying various anastomoses in the neck region, and reducing arterial pressure to 40-30 mm Hg by hemorrhage with subsequent reinfusion of the lost blood. RESULTS: In the postischemic period in the cat brain, control experiments showed the onset of metabolic acidosis and an increase in permeability of the brain capillaries to fluids and protein molecules. Intravenous introduction of losartan, an angiotensin II receptor antagonist, at a dose of 3 mg x kg(-1) 10 minutes into the postischaemic period, enhanced the normalization of metabolic and transcapillary exchange. Thus vector permeability was reversed from blood-to-tissue in the control situation (without losartan) to tissue-to-blood during losartan administration. CONCLUSIONS: The results provide strong evidence that losartan may play a role in preventing cerebral edema, and that the renin-angiotensin system plays an important role in postischemic cerebrovascular events.