Evaluation of "care of the foot" as a risk factor for diabetic foot ulceration: the role of internal physicians.

BACKGROUND AND OBJECTIVES: Several risk factors predispose the diabetic patient to foot ulceration, including "inadequate care of the foot". This risk factor for foot ulceration has not been previously evaluated among Nigeria diabetic patients and is the objective of this study. SUBJECTS AND METHODS: One hundred and twenty (120) diabetic patients with and without symptoms of peripheral neuropathy receiving care at the medical outpatient department (MOPD) and the diabetic clinic of the Nnamdi Azikiwe University Teaching Hospital Nnewi were recruited consecutively as they presented. They were administered structured questionnaires to assess some variables concerning care of their feet as provided to them by their physicians. RESULTS: Among the 120 diabetic participants, 83 (69.2%) had neuropathic symptoms (the symptomatic participants) while 37 (30.8%) were asymptomatic (the asymptomatic participants). Eighty (80; 96.4%) of the symptomatic vs 36 (97.3%) of the asymptomatic participants had never had their feet examined by their physician. Also, 26 (31.3%) of the symptomatic vs 12 (32.4%) of the asymptomatic participants had never received any form of advice on how to take special care of their feet by their physician, and 26 (31.3%) of the symptomatic vs 6 (16.2%) of the asymptomatic participants walked unshod most times in their immediate surroundings. CONCLUSION: Physicians do not provide adequate care to the feet of their diabetic patients irrespective of the presence or absence of neuropathic symptoms, making this variable a critical risk factor for diabetic foot ulceration and amputation. Continuing medical education to health care providers emphasizing adequate "care of the foot" of the diabetic patient, will reduce avoidable loss of limbs to diabetes.

Are the symptoms of diabetic peripheral neuropathy in Nigerian patients objective? An evaluation using the United Kingdom Screening Test (UKST) and Bio-Thesiometry.

BACKGROUND: Symptoms suggestive of peripheral neuropathy (PN) in diabetes mellitus (DM) do not always indicate presence ofunderlying PN. OBJECTIVE: A pioneering study among Nigerian diabetic subjects to evaluate the objectivity of their symptoms of PN using two objective diagnostic instruments for PN the United Kingdom Screening Test (UKST) and Bio-Thesiometry. SUBJECTS AND METHODS: One hundred and twenty diabetic participants and a similar number of non-diabetic controls were screened for symptoms of PN using the UKST symptoms score and subsequently separated into two groups those with symptoms ofPN and those without. The "symptomatic" cases and controls were further evaluated with the UKST signs score and Bio-Thesiometry to assess the objectivity of the symptoms. RESULTS: Among 120 diabetic participants, 83(69.2%) had neuropathic symptoms (the symptomatic cases) while 10 (8.3%) of the 120 non-diabetic controls had neuropathic symptoms (the symptomatic controls). Among the cases, UKST signs score detected PN in 89.2% (74/83) and Bio-Thesiometry 71.1% (59/83), the difference in the ability of the two methods to detect PN in this group being statistically significant (X2 = 8.51, df = 1, p < 0.01). Among the controls, UKST detected PN in 100.0% (10/10) compared to Bio-thesiometry (50.0%; 5/10), the difference in the ability of the two methods to detect PN in this group also being statistically significant (X2 = 4.27, df = 1, p < 0.05, using continuity correction factor). The difference in the ability of both methods to detect PN between the cases and controls was however not statistically significant (X2 = 0.68, df = 1, p > 0.3) CONCLUSION: The symptoms of PN among Nigerian diabetic subjects when evaluated with a gold standard for scoring the symptoms (the UKST symptoms score) are real, objective and truly indicate presence of underlying PN. Diabetic subjects presenting to medical clinics with symptoms of PN should receive serious attention and evaluation using this gold standard to detect early those with genuine PN and are at risk of foot ulceration from PN.

Is asymptomatic peripheral neuropathy present in Nigerian diabetic patients? An assessment using the United Kingdom screening test (UKST) and bio-thesiometry.

Diabetes mellitus (DM) is commonly complicated by peripheral neuropathy (PN). Symptoms suggestive of peripheral neuropathy (PN) in diabetes mellitus (DM) do not always indicate presence of underlying PN, while absence of symptoms does not rule out presence of underlying PN. To determine the prevalence of asymptomatic PN in diabetic patients using two methods--the United Kingdom Screening Test (UKST) and Bio-Thesiometry. 120 diabetic participants and a similar number of non-diabetic controls were screened for symptoms of PN using the UKST symptoms score and subsequently separated into two groups--those with symptoms of PN and those without. The "asymptomatic" cases and controls were further screened for underlying PN using the UKST signs score and Bio-Thesiometry Among 120 diabetic participants, 37 (30.8%) had no symptoms of PN (the asymptomatic cases) compared to 110 (91.7%) of the 120 non-diabetic controls (the asymptomatic controls). The UKST signs score detected PN more significantly among the cases than the controls (43.2% (16/37) vs 9.1% (10/110); /2 = 22.5, df = I, p < 0.01). Similarly, Bio-thesiometry detected PN more significantly among the cases than the controls (29.7% (11/37) vs 9.1% (10/110); X2 = 9.57, df = 1, p < 0.01) Asymptomatic PN is present among Nigerian diabetic subjects and the absence of "alarm" symptoms of PN does not exclude the presence of genuine PN.

Hepatitis C virus infection in Nigerians with diabetes mellitus.

BACKGROUND/AIMS: Studies from mainly Caucasian populations have shown epidemiological evidence of an association between diabetes mellitus and Hepatitis C virus (HCV) infection. The aim of this study was to determine whether any such association exists in a blackAfrican population with diabetes mellitus. METHOD: This was a cross sectional study of consecutive diabetic patients seen at the diabetes clinic of the University of Nigeria Teaching Hospital Enugu, Nigeria between September 1, 2004 and April 30, 2005. Patients who underwent upper gastrointestinal endoscopy during the same period for dyspeptic symptoms were used as controls after matching for age and sex. Structured questionnaire on risk factors for HCV infection was administered to the participants. Blood test for HCV antibodies was carried out on the diabetic patients as well as the control subjects. RESULTS: Out of 191 diabetic patients, 27(14.1%) were HCV antibody positive compared to the control group in which 5 out of 134 (3.7%) subjects had HCV antibodies (p = 0.0046). CONCLUSION: Hepatitis C virus infection is more common in Nigerian patients with diabetes mellitus than in control subjects. The nature of the association between diabetes mellitus and HCV infection remains to be elucidated.

H3Africa multi-centre study of the prevalence and environmental and genetic determinants of type 2 diabetes in sub-Saharan Africa: study protocol.

The burden and aetiology of type 2 diabetes (T2D) and its microvascular complications may be influenced by varying behavioural and lifestyle environments as well as by genetic susceptibility. These aspects of the epidemiology of T2D have not been reliably clarified in sub-Saharan Africa (SSA), highlighting the need for context-specific epidemiological studies with the statistical resolution to inform potential preventative and therapeutic strategies. Therefore, as part of the Human Heredity and Health in Africa (H3Africa) initiative, we designed a multi-site study comprising case collections and population-based surveys at 11 sites in eight countries across SSA. The goal is to recruit up to 6000 T2D participants and 6000 control participants. We will collect questionnaire data, biophysical measurements and biological samples for chronic disease traits, risk factors and genetic data on all study participants. Through integrating epidemiological and genomic techniques, the study provides a framework for assessing the burden, spectrum and environmental and genetic risk factors for T2D and its complications across SSA. With established mechanisms for fieldwork, data and sample collection and management, data-sharing and consent for re-approaching participants, the study will be a resource for future research studies, including longitudinal studies, prospective case ascertainment of incident disease and interventional studies.

Beta cell function and response to treatment in Nigerians with Type 2 diabetes mellitus.

There are scant data from African populations on the association between beta-cell function and response to treatment with oral hypoglycaemic agents in Type 2 diabetes mellitus (T2DM). Fasting plasma C-peptide (FCP) and glucagon-stimulated C-peptide (GSCP) levels were measured in 116 Nigerians with T2DM at a university teaching hospital. After 9 months of follow-up and treatment, they were categorized into three groups based on response to treatment: (A) good control but not on maximum sulphonylurea (SU) therapy, (B) inadequate control but not on maximum SU therapy and (C) on maximum SU therapy+/-insulin or biguanide. Logistic regression models were used to investigate how well C-peptide levels predicted the subjects belonging to Group C who are likely to require insulin. The mean FCP and mean GSCP levels of Group C were significantly lower than in the other groups (p=0.024; p= <0.001 respectively). A GSCP cut-off value of < or =1.3 ng/mL predicted membership of Group C with 85% sensitivity and 89% specificity while a cut-off of < or =1.8 ng/mL was associated with 91% sensitivity and 66% specificity. In resource-poor settings where inadequate treatment are common, estimation of GSCP may be useful in predicting treatment response and should be weighed against the cost of inadequate therapy with higher morbidity and mortality.

In search of susceptibility genes for type 2 diabetes in West Africa: the design and results of the first phase of the AADM study.

PURPOSE: The purpose of this study is to map type 2 diabetes susceptibility genes in West African ancestral populations of African-Americans, through an international collaboration between West African and US investigators. DESIGN AND METHODS: Affected sib-pairs (ASP) along with unaffected spouse controls are being enrolled and examined in West Africa, with two sites established in Ghana (Accra and Kumasi) and three in Nigeria (Enugu, Ibadan, and Lagos). Eligible participants are invited to study clinics to obtain detailed epidemiologic, family, and medical history information. Blood samples are drawn from each participant to measure glucose, insulin, C-peptide, total cholesterol, LDL, HDL, triglycerides, albumin, creatinine, urea, uric acid, total calcium and to detect autoantibodies to glutamic acid decarboxylase (GAD). DNA is isolated from frozen white blood cells obtained from 20 ml of EDTA whole blood samples. RESULTS: With full informed consent, 162 individuals from 78 families have been enrolled and examined since the Africa America Diabetes Mellitus (AADM) study began in June of 1997. Logistics of field examinations and specimen shipping have been successfully established. At the end of the third year of field activity (September 2000) the AADM study will have enrolled and performed comprehensive examination on 400 ASP with type 2 diabetes, for a minimum of 800 cases and 200 controls from Ghana and Nigeria. At the current participation rate, the goal of 400 sib-pairs and 200 controls will be met before the scheduled closing date. CONCLUSIONS: The AADM study will create a comprehensive epidemiologic and genetic resource that will facilitate a powerful genome-wide search for West African susceptibility genes to type 2 diabetes.

Diabetes mellitus in pregnancy in an African population.

OBJECTIVES: To compare the pregnancy outcome among diabetic and non-diabetic Nigerian women. METHODS: A retrospective case record review of 200 pregnant diabetic patients and control was carried out over a 10-year period (1990-1999) at the Maternity unit of the University of Nigeria Teaching Hospital Enugu, Nigeria. RESULTS: The prevalence of diabetes mellitus among pregnant mothers was 1.7%. Pre-gestational diabetes mellitus accounted for 39% of cases while gestational diabetes was responsible for 61% of them. Late antenatal booking and poor control of diabetes mellitus were common features, while maternal and fetal morbidity was high. Hypertension, vulvovaginitis, premature labor, polyhydramnios and ketoacidosis were significantly higher among diabetic mothers than controls. The perinatal mortality was also higher among diabetics than controls (12.5% vs. 3.5%) with stillbirth being the major contributor. Patients with gestational diabetes were at increased risk of fetal macrosomia than controls (28.7% vs. 5.5%). The overall cesarean section rate was high (36%) among diabetics with previous cesarean section and cephalopelvic disproportion being the commonest indications. CONCLUSIONS: Health education and provision of modern affordable methods of management of diagnosed cases such as uristix and hemastix will improve maternal and fetal outcome in pregnant diabetics in Africa.

Biochemically unmonitored treatment of diabetic ketoacidosis for the first eight hours using the low dose intra-muscular insulin regimen: preliminary report.

The clinical efficacy of frequent low dose intra-muscular insulin in treating diabetic ketoacidosis was tested in eight patients who presented over a period of nine months. Blood sugar, urea and electrolytes were estimated only at presentation and eight hours after commencing insulin therapy instead of the initial one to two hourly estimations usually advocated. All the patients responded satisfactorily by eight hours despite the infrequent monitoring of blood sugars, urea and electrolytes. No hypoglycaemic episodes or clinical evidence of hypokalaemia were encountered. It is suggested that where facilities and staffing are inadequate, as in some developing countries, the first eight hours of treatment of diabetic ketoacidosis can be safely carried out using the frequent intramuscular low dose insulin regimen without much emphasis laid on monitoring the blood sugar, urea and electrolytes, provided there are no contraindicating cardio-pulmonary or renal diseases.

Circulating adiponectin is associated with renal function independent of age and serum lipids in west africans.

Adiponectin, a protein secreted by adipose tissue, has been associated with renal dysfunction. However, these observations have not been adequately investigated in large epidemiological studies of healthy individuals in general and in African populations in particular. Hence, we designed this study to evaluate the relationship between adiponectin and renal function in a large group of nondiabetic West Africans. Total adiponectin was measured in 792 participants. MDRD and Cockroft-Gault (CG-) estimated GFR were used as indices of renal function. Linear and logistic regression models were used to determine the relationship between adiponectin and renal function. Adiponectin showed an inverse relationship with eGFR in univariate (Beta(MDRD) = -0.18, Beta(CG) = -0.26) and multivariate (Beta(MDRD) = -0.10, Beta(CG) = -0.09) regression analyses. The multivariate models that included age, sex, BMI, hypertension, smoking, HDL-C, LDL-C, triglycerides, and adiponectin explained 30% and 55.6% of the variance in GFR estimated by MDRD and CG methods, respectively. Adiponectin was also a strong predictor of moderate chronic kidney disease (defined as eGFR < 60 mL/min/1.73 m(2)). We demonstrate that adiponectin is associated with renal function in nondiabetic West Africans. The observed relationship is independent of age and serum lipids. Our findings suggest that adiponectin may have clinical utility as a biomarker of renal function.

Basal insulin resistance and secretion in Nigerians with type 2 diabetes mellitus.

AIM: The objective of this study was to estimate basal insulin resistance (IR) and insulin secretion (IS) in Nigerians with type 2 diabetes mellitus (T2DM). METHODS: The homeostasis model assessment (HOMA) method was used to estimate basal IR and IS in 146 Nigerians with T2DM and in 33 controls at the University of Nigeria Teaching Hospital (UNTH), Enugu, Nigeria. Correlations and multiple regression analysis between Box-Cox-transformed IR and log-transformed IS and anthropometric indices were carried out. RESULTS: IR and reduced IS were present, respectively, in 139 (95.5%) and 109 (74.7%) of the diabetic subjects and in 25 (75.8%) and 4 (12.1%) of the controls. In the diabetic subjects, age at diagnosis, duration of diabetes, waist circumference (WC), and body mass index (BMI) correlated significantly with IR (r = -0.2399, P = 0.0035; r = 0.1993, P = 0.0166; r = 0.2267, P = 0.0059; r = 0.2082, P = 0.0120; respectively), whereas duration of diabetes, WC, and BMI correlated significantly with IS (r = -0.2166, P = 0.0091; r = 0.3062, P = 0.0002; r = 0.2746, P = 0.0008; respectively). Age at diagnosis, WC, and duration of diabetes were significant predictors of IR (beta = -0.0161, P < 0.001; beta = 0.0121, P = 0.002; beta = 0.0138, P = 0.042; respectively), whereas duration of diabetes and WC significantly predicted IS (beta = -0.0159, P = 0.025; beta = 0.0155, P < 0.001). CONCLUSIONS: This study shows that both IR and reduced IS are major features of T2DM in Nigerians and that WC consistently correlated and predicted IR. WC measurement is simple and ideal in resource-poor settings for the detection of IR and abdominal obesity. The apparent rarity of coronary heart disease (CHD) in black Africans with T2DM despite a high prevalence of IR warrants further investigation.

Agouti-related protein promoter variant associated with leanness and decreased risk for diabetes in West Africans.

OBJECTIVE: The role of the central melanocortin system in the development of obesity has been extensively studied. Single-nucleotide polymorphisms (SNPs) within several candidate genes have been associated with food intake and obesity-related phenotypes; however, few of these associations have been replicated. SNPs in the agouti-related protein (AGRP) gene coding (Ala67Thr, 199G/A) and promoter (-38C/T) have been reported to be associated with body mass index (BMI), fat mass (FM) and percent body fat, in populations of European and African descent. In this study, we evaluated the association between the functional AGRP -38C/T promoter SNP and weight-related traits, namely BMI, FM and fat-free mass (FFM), as well as diabetes status. DESIGN: An association study of the AGRP -38C/T SNP and indices of obesity and diabetes status. SUBJECTS: A well-characterized population of 538 West Africans from Ghana and Nigeria recruited in the AADM (Africa America Diabetes Mellitus) study (mean age 52 years, 41.3% males, 71% diabetic). MEASUREMENTS: Genotyping of the AGRP -38C/T SNP, BMI, FM, FFM and fasting plasma glucose. RESULTS: Women carrying two copies of the variant T allele had significantly lower BMI (OR=0.47; 95% CI, 0.25-0.87). Also, men with at least one copy of the variant T allele were over two times less likely to be diabetic than other men (OR=0.44; 95% CI, 0.22-0.89). CONCLUSION: Our results replicate previous findings and implicate the AGRP -38C/T SNP in the regulation of body weight in West Africans.

A genome-wide scan for quantitative trait loci linked to obesity phenotypes among West Africans.

OBJECTIVE: To identify quantitative trait loci (QTL) for three obesity phenotypes: body mass index (BMI), fat mass (FM) and percent body fat (PBF) in West Africans with type 2 diabetes (T2DM). DESIGN: An affected sibling pair (ASP) design, in which both siblings had T2DM. Obesity was analyzed as a quantitative trait using a variance components approach. SUBJECTS: Sib-pairs affected with T2DM from the Africa America Diabetes Mellitus (AADM) study, comprising 321 sibling pairs and 36 half-sibling pairs. MEASUREMENTS: Weight was measured on an electronic scale to the nearest 0.1 kg, and height was measured with a stadiometer to the nearest 0.1 cm. Body composition was estimated using bioelectric impedance analysis (BIA). Genotyping was carried out at the Center for Inherited Disease Research (CIDR) with a panel of 390 trinucleotide and tetranucleotide repeats. RESULTS: The obesity-related phenotype showing the strongest linkage evidence was PBF on chromosome 2 (LOD 3.30 at 72.6 cM, marker D2S739). Suggestive linkage to FM was found on chromosomes 2 (LOD 2.56 at 80.4 cM) and 5 (LOD 2.25 at 98 cM, marker D5S1725). The highest LOD score for BMI was 1.68 (chromosome 4, 113.8 cM). The areas of linkage for the three phenotypes showed some clustering as all three phenotypes were linked to the same regions of 2p13 and 5q14, and our study replicated linkage evidence for several regions previously reported in other studies. CONCLUSION: We obtained evidence for several QTLs on chromosome 2, 4 and 5 to three obesity phenotypes. This study provides data on the genetics of obesity in populations that are currently under represented in the global effort directed at understanding the pathophysiology of excess adiposity in free living individuals.

Remittant diabetes mellitus in Nigeria.

Forty three newly diagnosed non-obese Nigerian diabetic patients (20 males and 23 females), who required insulin for initial control, were left without dietary control and were followed up for a minimum period of one and half years in each case. Four patients (9.3%) are in true remissions up to the time of writing. Eight other patients (18.6%) went through varying periods of apparent remissions of between three months and 19 months. It seems that even non-obese Nigerian diabetics may remit despite a free diet and initial need for insulin. The reasons for diabetic remissions remain largely unexplained but may be related, in Nigeria, to the aetiological nature of diabetes mellitus in this part of the world.

Pathogenesis of juvenile tropical pancreatitis syndrome.

The name juvenile tropical pancreatitis syndrome (JTPS) is proposed for a disease which affects young people of both sexes in certain parts of the tropics and which is characterised by abdominal pain, diabetes, steatorrhoea, and pancreatic calcification. The condition seems to start with blockage of the pancreatic ducts by laminated secretions or inspissated mucus plugs which later calcify. Chronic pancreatitis follows. The hypothesis is that plugs are the result of pancreatic stasis due to prolonged lack of food in the stomach and/or gastroenteritis and dehydration. Most plugs are probably dislodged during convalescence when protein-containing foods are eaten and stimulate vigorous flow of pancreatic juice. The sluggish pancreatic flow produced by very-low-protein diets may not dislodge plugs. Repeated infection and anorexia can enlarge the plugs which ultimately calcify. JTPS therefore occurs in Third-World areas with a high rate of childhood infections, and where low-protein staples are taken. Cereal staples seem to reduce the incidence of JTPS in endemic areas because of their protein content.

Do Nigerian diabetics with haemoglobin genotype Hb AS have greater risks of developing renal complications and hypertension? A preliminary report.

Thirty nine non-insulin dependent Nigerian diabetics (21 males and 18 females) aged 40-63 years (mean 50.6 years) with haemoglobin genotype Hb AA who had diabetes for 5-8 years were matched with an equal number of non-insulin dependent diabetics with haemoglobin genotype Hb AS for sex, age, duration of diabetes and state of control of diabetes. The occurrence of proteinuria and hypertension was studied in all patients; serum creatinine and 24 hour urine protein excretion were measured in those with proteinuria. Eight of the 39 diabetics with Hb AS had developed significant proteinuria compared to two with Hb AA (p less than 0.05). The serum creatinine was constantly above 2.0 mg/100 ml in four of the eight diabetics with Hb AS compared to one with Hb AA, whilst the 24 hour protein excretion in the urine was above 2.0 g in three diabetics with Hb AS compared to none with Hb AA. Twelve diabetics with Hb AS had hypertension compared to three with Hb AA (p less than 0.01). These results suggest that Nigerian diabetics with haemoglobin genotype Hb AS may have greater risks of developing proteinuria, with renal dysfunction and/or hypertension and probably diabetic nephropathy than their counterpart with haemoglobin genotype Hb AA.