Clinical, Metabolic and Immunological Characteristics of Ghanaian Patients with Diabetes Mellitus

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Febuary, 2009
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Objectives: This study investigated the clinical characteristics of Ghanaian diabetic patients; prevalence of metabolic syndrome and its components in Ghanaian diabetic patients; and determinants of the metabolic syndrome diagnosed from Ghanaian diabetic patients. Further, association of metabolic syndrome with poor glycaemic control and occurrence and features of autoimmune diabetes and autoantibody-negative type 2 diabetes in Ghanaian diabetic patients were investigated. Research design and methods: This research was a prospective study covering a period of four years, from August 2004 to June 2008. The study was carried out at the Komfo Anokye Teaching Hospital and the Kwame Nkrumah University of Science and Technology, both in Kumasi on two study populations. For the first population, Ghanaian diabetic patients diagnosed by the WHO criteria were consecutively selected. The sample size was 456. Controls included 120 age- and sex-matched nondiabetic controls. For the second population, recently diagnosed (<1 year) Ghanaian diabetic patients were consecutively selected. The sample size was 120. Controls included 60 age- and sex-matched healthy nondiabetic controls. Socio-demographic and clinical characteristics of subjects were investigated using a standardized questionnaire. Blood pressure and anthropometric measurements (height, weight, waist circumference) of subjects were measured using mercury sphygmomanometer, physician standiometer and scale and a plastic tape respectively. Blood and serum samples from subjects were analysed for relevant biochemical indices using enzymatic methods and ATAC® 8000 Random Access Chemistry Analyzer and its reagent kits. Metabolic syndrome was diagnosed using the National Cholesterol Education Programme Adult Treatment Panel III (NCEP ATP III) criteria. HbA1C was analysed using an inhibition of latex agglutination test, DCA® 2000+ analyzer (Bayer model, USA) and its reagent kits. Insulin and autoantibodies were tested using an Enzyme linked immunosorbent assay (ELISA) technique, DRG International Inc. USA EIA reagent kits, ELISA reader (Tipo model, Italy) and washer (Murex, Great Britain). iii Results: The sex distribution of the Ghanaian diabetic patients of the first study population was 30.9% males and 69.1% females. Insulin-requiring diabetics were 24.6% and non-insulin requiring diabetics 75.4%. The mean age was 55.8 ± 12.3 years; 90.6% were ≥40 years of age. The mean age of onset was 49.7 ± 12.5 years; 89.5% had an age of onset ≥35 years or late onset diabetes. The mean diabetes duration was 6.0 ± 5.4 years and 60.5% had diabetes duration 1 – 9 years. Mean preprandial (fasting) glucose level was 9.4 ± 4.5 mmol/L with 62.1% having high preprandial glucose >7.2 mmol/L. The mean BMI was 25.1 ± 4.8 kg/m2; 44.5% were overweight and obese or had a BMI ≥25.0 kg/m2. The mean waist circumference was 87.0 ± 13.7 cm; 43.6% had central obesity. Diabetics with confirmed hypertension were 40.1%; hypertensives with inadequate blood pressure control ≥130/80 mmHg were 91.3%. The prevalence of the metabolic syndrome was 55.9% in the first population; prevalence in females (66.0%) was higher than males (33.3%). Low HDL cholesterol was the commonest component (47.4%) of the metabolic syndrome in the first population, followed by hypertension (46.9%). In females central obesity (57.1%) was the commonest component, followed by low HDL cholesterol (53.0%); in males, hypertension (39.7%) was the commonest component, followed by hypertriglyceridaemia (36.2%). Central obesity, hypertension and low HDL cholesterol prevalence was higher in females than males, while hypertriglyceridaemia prevalence was comparable in females and males. Female diabetics individually carried more metabolic syndrome factors than males. The major determinant of the metabolic syndrome diagnosed from Ghanaian diabetics was central obesity (69.4%) followed by hypertension (67.5%). In females the major determinant was central obesity (76.9%), followed by hypertension (67.3%), while in males the major determinant was hypertriglyceridaemia (74.5%), followed by hypertension (68.1%). The most frequent combination of different components was hyperglycaemia, central obesity and hypertension (46.3%). For the second population, the prevalence of the metabolic syndrome in patients with poor glycaemic control was 50.0% and patients with good glycaemic control 33.3%. The prevalence of autoimmunty in the insulin-requiring recently diagnosed diabetic patients was 35.3% and in the non-insulin requiring patients 16.5%. The prevalence of LADA in the non-insulin requiring diabetic patients was iv 13.5%. The prevalence of LADA and autoimmune type 1 diabetes in the second population were 11.7% and 7.5% respectively, giving total autoimmune diabetes prevalence of 19.2%; single autoantibody positivity was 77.3% and multiple autoantibody positivity 22.7% in the autoimmune diabetic patients. Most of the clinical and metabolic parameters of autoimmune diabetes and type 2 diabetes did not differ. The exceptions were hypertension and central obesity which were more likely in type 2 diabetes than autoimmune diabetes and HbA1C which was higher in autoimmune diabetes than type 2 diabetes. Conclusion: There were more Ghanaian females with diabetes mellitus than males and more non-insulin requiring than insulin requiring patients. Majority of the diabetic patients were 40 years and above and had late onset diabetes. More than half had diabetes disease duration of 1-9 years and carry clinical modifiable risk factors for microvascular and macrovascular disease. Less than half of the subjects had clinical modifiable risk factors for cardiovascular disease. The metabolic syndrome was frequent in Ghanaian diabetic patients, especially females, and was present at an prevalence slightly less than that in developed countries. Future prevention and control strategies should not overlook the importance of metabolic disease risk factors in Ghana. Interventions that address obesity and hypertension in females and hypertriglyceridaemia and hypertension in males and reduce waist circumference, blood pressure and hypertriglyceridaemia, may reduce the prevalence of the metabolic syndrome, and hence cardiovascular disease in Ghanaian diabetic patients. The major determinants of the metabolic syndrome were not necessarily the commonest metabolic syndrome components of the population under consideration. The metabolic syndrome was associated with poor glycaemic control. However, metabolic syndrome and poor glycaemic control are independent risk factors for cardiovascular disease. Autoimmune diabetes, including autoimmune type 1 diabetes and LADA, occurs in recently diagnosed Ghanaian diabetic patients. Both ICA and GAD autoantibody tests are required to identify autoimmune diabetes, and distinguish it from autoantibody-negative type 2 diabetes. Clinical and metabolic markers cannot be used for this purpose.
A Thesis Submitted to the Department of Molecular Medicine, Kwame Nkrumah University of Science and Technology in Fulfillment of the Requirement for the Degree Of Doctor of Philosophy in Chemical Pathology.