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Biomedical subjects

A A Motala

Publications and source records attributed to A A Motala.

At least 19 recordsLinked to original sources

Toll-like receptor 3 gene polymorphisms in South African Blacks with type 1 diabetes.

Type 1 diabetes is the consequence of exposure of genetically susceptible individuals to specific environmental precipitants. The innate immune system provides the initial response to exogenous antigen and links with the adaptive immune system. The aim of this study was to assess the role of polymorphisms occurring in the cytoplasmic region of toll-like receptor (TLR) 3 gene and immediate 5' sequence, in subjects of Zulu descent with type 1 diabetes in KwaZulu-Natal, South Africa. Seventy-nine subjects with type 1 diabetes and 74 healthy normal glucose tolerant gender-matched control subjects were studied. Parts of exon 4 and exon 3/intron 3 of the TLR3 gene were studied by polymerase chain reaction, direct sequencing and restriction enzyme digestion with Bts 1. Of the nine polymorphisms studied, a significant association with type 1 diabetes was found for the major allele in the 2593 C/T polymorphism and for the minor alleles in the 2642 C/A and 2690 A/G polymorphisms, which were found to be in complete linkage disequilibrium. Correction of the P-values for the number of alleles studied, however, rendered the results no longer significant. These results suggest that polymorphisms in the TLR3 gene, which is part of the innate immune system, may be associated with type 1 diabetes in this population.

Adult↗

High incidence of Type 2 diabetes mellitus in South African Indians: a 10-year follow-up study.

AIMS: Previous cross-sectional studies have established that South African Indians have a high prevalence of Type 2 diabetes mellitus. A prospective community study was undertaken to determine the incidence of Type 2 diabetes and the risk factors associated with its development in a cohort of South African Indians who had been studied 10 years previously. METHODS: This is a report on 563 subjects who participated both at baseline and at the 10-year follow-up study. In the baseline study, 2479 subjects (> 15 years) were studied; using 1985 World Health Organization criteria for glucose tolerance based on 75 g oral glucose tolerance tests (OGTT), the crude prevalence of diabetes mellitus (Diabetes) was 9.8% and of impaired glucose tolerance (IGT) 5.8% (age and sex-adjusted prevalence 13% and 6.9%, respectively). RESULTS: At the 10-year follow-up study, 563 of the subjects who could be traced consented to a repeat OGTT; of these, 91 (16.2%) were classified as Diabetes and 41 (7.3%) as IGT. Of the subjects who did not have diabetes at baseline (n = 517), 49 (9.5%) progressed to diabetes (PTD) and 40 (7.7%) had IGT. The crude cumulative incidence of diabetes was 9.5% (rate of progression 0.95% per annum; incidence density 9.5/1000 person years) with an age and sex-adjusted cumulative incidence of 8.3% (rate of progression 0.95% per annum; incidence density 8.3/1000 person years). Examination of risk factors predictive of subsequent diabetes development was undertaken by analysis of baseline (year 0) variables in the 517 subjects who did not have diabetes at baseline. In multivariate analysis using a logistic regression model, the significant predictive risk factors for future diabetes included 2-h post load plasma glucose (2 PG) (P < 0.0001, odds ratio (OR) 1.7, 95% confidence interval (CI) 1.4-2.1), body mass index (BMI) (P < 0.006, OR 1.1, 95% CI 1.0-1.3) and obesity (P < 0.01, OR 4.6, 95% CI 1.4-14.7). CONCLUSIONS: This long-term study has shown that in South African Indians there is a high incidence of Type 2 diabetes, and in this population significant predictors include higher baseline blood glucose, BMI and obesity.

Asia↗

HLA class II antigens in South African Blacks with type I diabetes.

Type 1 diabetes mellitus is poorly characterised in many African communities, including South Africa, where little is known of the disease epidemiology. This study aimed to identify the HLA class II alleles associated with type 1 diabetes in a group of Zulu subjects in Durban, KwaZulu-Natal by PCR-SSP. The HLA alleles associated with type 1 diabetes included HLA-DQB*0302 (P<0.0001), DRB1*O9 (P<0.0001), DRB1*04 (P=0.002), DRB1*0301 (P=0.003), DQB*02 (P=0.004) and DQA*03 (P=0.035). Estimated haplotypes positively associated with type 1 diabetes included HLA-DRB1 *0301-DQA*0501, DRB1*04-DQA*03, DRB1*04-DQB*0302, DRB1*0301-DQB*0201, DQA*0501-DQB*0201 and DQA*03-DQB*0302. These findings are similar to those reported from Zimbabwe and other populations with type 1 diabetes.

Adult↗

Microvascular complications in South African patients with long-duration diabetes mellitus.

OBJECTIVE: To determine the prevalence of microvascular complications in South African black and Indian patients with long-duration diabetes mellitus (DM). DESIGN: A retrospective analysis was undertaken of clinical records of 219 DM patients (132 black, 87 Indian) with long-duration DM (over 10 years) attending a diabetes clinic in Durban. Data recorded on each subject included demographic details (age, gender, ethnic group, type of diabetes, age of onset and duration of diabetes), presence of retinopathy, markers of nephropathy and biochemical variables. The prevalence of complications and the clinical and biochemical parameters were evaluated for type 1 and type 2 diabetes and for each ethnic group. RESULTS: Of the 219 patients, 47 had type 1 DM (36 blacks, 11 Indians) and 172 were classified as type 2 DM (96 blacks, 76 Indians). The mean age of onset of DM was later in blacks than Indians, both for type 1 (P < 0.05) and type 2 DM (P < 0.01). In patients with type 1 DM, the prevalence of retinopathy was 53.2% (blacks 55.6%, Indians 45.5%), persistent proteinuria was found in 23.4% (blacks 25%, Indians 18.2%) and hypertension in 34%. No ethnic difference was found except for the prevalence of hypertension which was higher in blacks than Indians (41.7% v. 9.1%, P < 0.5). Onset of retinopathy from time of diabetes diagnosis occurred earlier in blacks than Indians (13.0 +/- 4.6 yrs v. 18.0 +/- 4.6 yrs, P < 0.05). For the type 2 DM group, retinopathy was found in 64.5% (black v. Indian 68.8 v. 59.2%) and persistent proteinuria in 25% (black v. Indian 30.2 v. 18.4%). Hypertension was observed in 68% and was more prevalent in blacks (84.4 v. 47.4%, P < 0.01) There was an earlier onset of retinopathy (P < 0.05) and hypertension (P < 0.01) from time of diabetes diagnosis in blacks than Indians. In the type 1 DM group retinopathy was associated with a significantly longer duration of diabetes (P < 0.05) and higher glycated haemoglobin (HbA1) (P < 0.05). For type 2 DM subjects there was a significant association between retinopathy and longer duration of diabetes (P < 0.05) and higher systolic blood pressure (P < 0.05). CONCLUSION: This study has shown that there is a high prevalence of microvascular complications in South African patients with long-duration diabetes mellitus.

Adult↗

Application of the new ADA criteria for the diagnosis of diabetes to population studies in sub-Saharan Africa. American diabetes association.

AIMS: To examine the implications for epidemiological studies of the American Diabetes Association (ADA) recommendation that the fasting blood glucose at a lowered level becomes the main diagnostic test for diabetes on cross-sectional-based data from sub-Saharan Africa. METHODS: Data from 11 surveys conducted in rural, peri-urban and urban Cameroon (n = 1804), South Africa (n = 3799) and Tanzania (n = 10013) which measured fasting (ADA criteria) and 2-h blood glucose concentrations during a standard 75 g OGTT (old WHO criteria) were analysed. RESULTS: The prevalence of diabetes was higher in eight of the 11 surveys when applying the new ADA compared to the old WHO criteria. With the exception of one population (Mara, Tanzania) the absolute difference in prevalence between the two classifications tended to be small (< 2%). There was considerable variation in the categorization of individuals using the ADA and old WHO criteria. The level of agreement between the two ranged from fair to good (Kappa statistic 0.17-0.86). The prevalence of impaired fasting glycaemia (IFG) was lower than that of impaired glucose tolerance (IGT) in 10 of the surveys and the agreement between the two was fair, < or = 0.26 in all the surveys. CONCLUSIONS: Although the use of the new ADA fasting criteria for prevalence surveys is an attractive and practical option, particularly in Africa, further information is required on the characteristics and prognosis of individuals classified as IFG or diabetic by the fasting criteria, prior to wide adoption of the ADA criteria. Ideally measurement of both fasting and two low glucose concentrations should remain the standard for epidemiological studies.

Adult↗

Transient impaired glucose tolerance in South African Indians does not carry a risk for progression to NIDDM.

OBJECTIVE: To evaluate the significance of transient impaired glucose tolerance (IGT) in terms of the risk of progression to NIDDM and the serum insulin response during oral glucose tolerance test (OGTT) in a prospective study on the natural history of IGT in South African Indians. RESEARCH DESIGN AND METHODS: This is a report on 87 subjects who formed part of a 4-year prospective study in 128 subjects classified with IGT at baseline (year 0) using World Health Organization criteria for glucose tolerance. Subjects were reexamined at years 1 and 4. At year 1, based on OGTT results, the subjects were divided into three groups: transient IGT (normal glucose tolerance [trIGT], n = 40), persistent IGT (pIGT, n = 47), and diabetes (n = 41). Analysis was performed on the 87 subjects who were classified as IGT at year 0, but who had not progressed to NIDDM by year 1 of the study At baseline (year 0), a modified OGTT was performed; between years 1 and 4, the OGTT included timed midtest samples for plasma glucose and serum insulin. Analysis of predictive factors for progression to diabetes or reversion to normal glucose tolerance was undertaken using year 0 as baseline. RESULTS: By year 4, 72 subjects (82.8%) completed the study Of the 32 subjects in the trIGT group, none (0%) had progressed to NIDDM, 11 (34.4%) had reverted to IGT (N-IGT), and 21 (65.6%) had persisted with normal glucose tolerance (N-N); of the 40 subjects in the pIGT group, 16 (40%) had progressed to NIDDM (IGT-D), 17 (42.5%) had persisted with IGT (IGT-IGT), and 7 (17.5%) had reverted to normal glucose tolerance (IGT-N). Significant predictive factors for reversion to normal glucose tolerance included absence of obesity (P = 0.0131, odds ratio [OR] 4.2, 95% CI 1.4-13.1) and 2-h plasma glucose level (P = 0.027, OR 2.4, 95% CI 1.11-5.13) at baseline (year 0). Intergroup (cross-sectional) analysis showed that the serum insulin response was higher in the pIGT than in the trIGT subgroup (fasting serum insulin: IGT-N vs. N-IGT and N-N, 16.9 +/- 1.9 vs. 6.8 +/- 2.1 and 6.1 +/- 2.4 microU/ml, respectively, P < 0.001; 2-h postload serum insulin: IGT-IGT vs. N-IGT, 116.8 +/- 2.2 vs. 60.3 +/- 1.7 microU/ml, P < 0.05). By contrast, the insulinogenic index was higher in the trIGT subgroups both at year 1 (90-min: N-N vs. IGT-D, 48.9 +/- 3.9 vs. 14.1 +/- 2.5; P < 0.05) and at year 4 (N-N vs. remaining four subgroups, P < 0.01 at 60 min and 90 min). Intragroup (prospective) comparisons showed that in the N-IGT subgroup, the mean 2-h insulinogenic index was lower at year 4 than at year 1 (19.9 +/- 1.7 vs. 66.0 +/- 2.7; P < 0.05). CONCLUSIONS: In this 4-year prospective study in South African Indians, transient IGT carries no risk of progression to NIDDM. The significant predictive factors for reversion to normal glucose tolerance include lower baseline obesity prevalence and 2-h postload plasma glucose level. Moreover, in this group, beta-cell secretory function appeared to deteriorate with worsening of glucose tolerance.

Adult↗

The significance of a positive family history in South African Indians with non-insulin-dependent diabetes (NIDDM).

A group of South African Indians with NIDDM participated in a study to evaluate the frequency of positive family histories of the disease and to determine the relative contribution of maternal or paternal genetic determinants. Information was elicited by means of an interview and recorded. Of the 1098 diabetic subjects studied 70% gave a positive family history of a first degree relative suffering from NIDDM. Three-generation transmission was recorded in 5.3% of the subjects. A significantly greater proportion of probands (40%) had a mother with NIDDM than those with a father (26%). A positive family history in an offspring was more common in female probands (10.6%) than males (5.5%). Twice as many probands with 3 generation transmission had a maternal grandmother suffering from NIDDM (2.5%) compared with those who had a paternal grandmother afflicted (1.2%) (P < 0.05), whereas the frequencies in the maternal (0.9%) and paternal (0.8%) grandfathers were similar. This study has highlighted, not only the high prevalence of a positive family history in South African Indians with NIDDM, but also a stronger maternal contribution to the putative gene responsible for the disease.

Chi-Square Distribution↗

Evaluation of WHO and NDDG criteria for impaired glucose tolerance.

A 4-year prospective study on the natural history of IGT in South African Indians has allowed for the evaluation of the WHO and NDDG criteria for IGT, using the five groups for non-diabetic glucose tolerance recently recommended and relating these to the risk of diabetes development. Using WHO criteria, 128 subjects were classed IGT in a baseline survey (Year 0). The five recommended categories were applied to the OGTTs done between Year 1 and Year 4 of the study, when mid-test plasma (MPG) samples were also obtained. These categories included N-N (Normal by WHO and NDDG); N-ND1 (Normal by WHO, non-diagnostic level 1 by NDDG); N-ND2 (Normal by WHO, non-diagnostic level 2 by NDDG); I-ND3 (IGT by WHO, non-diagnostic level 3 by NDDG) and I-I (IGT by WHO and NDDG). The risk of diabetes development and the significance of the non-diagnostic category were evaluated by comparing the glucose tolerance status at Year 4 with the status at Year 1. In the cross-sectional evaluation at Year 1, of the 87 non-diabetic OGTTs analysed, 31% (n = 27) were classified I-I, 34.5% (n = 30) were classed N-N and 34.5% (n = 30) were classified non-diagnostic [I-ND3 (23.1%); N-ND2 (8%); N-ND1 (3.4%)]. In the prospective analysis, of the 72 subjects who completed the study, 16 subjects developed NIDDM by Year 4; of these 13 subjects were classed I-I and 3 subjects I-ND3 at Year 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

Evidence for impaired pancreatic beta cell function in South African Indians with impaired glucose tolerance.

In a prospective study of South African Indians with impaired glucose tolerance (IGT), the serum insulin response during a 75 g oral glucose tolerance test (OGTT) was examined in 128 subjects who were classified as IGT 1 year previously (year 0) and in 60 matched control subjects. Based on the results at year 1, study subjects were divided into three groups, using World Health Organization criteria for glucose tolerance: IGT (n = 47), diabetes (n = 41), and transient IGT (normal glucose tolerance) (n = 40). When compared with the control group, despite higher plasma glucose concentrations, the IGT group showed similar fasting insulin, but lower 30-min insulin response (57.4 +/- 1.9 mUl-1 vs 86.5 +/- 1.8, p < 0.001) and lower 30-min insulin/glucose ratio (7.4 +/- 5.2 vs 13.3 +/- 8.7, p < 0.001). The insulinogenic index was lower in the IGT group than in the control group at 30, 60, 90, and 120 min (p < 0.01, p < 0.001, p < 0.001, p < 0.001, respectively). The 2-h insulin response was higher in the IGT group (106.7 +/- 1.9 mUl-1 vs 59.2 +/- 1.9, p < 0.01). The IGT group displayed a delayed pattern of insulin response with maximum levels only at 2-h. Insulin area was similar in the two groups. In the transient IGT group, despite similar plasma glucose levels, the insulin responses at 0, 15, 30, and 60 min (p < 0.01, p < 0.001, p < 0.001, p < 0.001, respectively) were lower than in the control group; the 30-min insulin/glucose ratio (7.1 +/- 5.1 vs 13.3 +/- 8.7, p < 0.001) and 60-min insulinogenic index (46.9 +/- 86.3 vs 123.4 +/- 206.3, p < 0.001) were also lower in the transient IGT group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

South African Indians show a high prevalence of NIDDM and bimodality in plasma glucose distribution patterns.

OBJECTIVE: To determine the prevalence of diabetes mellitus and impaired glucose tolerance (IGT) and to test for bimodality in the plasma glucose distribution in South African Indians. RESEARCH DESIGN AND METHODS: Subjects were selected by systematic cluster sampling in various areas of Durban. They underwent a modified glucose tolerance test whereby fasting and 2-h postglucose (75 g) plasma glucose levels were measured. The program MIX was used to test for bimodality in the plasma glucose distribution. RESULTS: We tested 2,479 subjects (1,441 women and 1,038 men). Based on the revised World Health Organization criteria, the crude prevalence of diabetes mellitus was 9.8%, and the crude prevalence of IGT was 5.8%; the age- and sex-adjusted prevalence was 13.0 and 6.9%, respectively. IGT was significantly more common in men (7.6%) than in women (4.4%). Obesity was a feature of both diabetes mellitus and IGT, particularly in women. Both fasting and 2-h plasma glucose values did not conform to a single normal distribution pattern in any age-group, whereas unequivocal evidence of bimodality was seen in the 55- to 74-year age-group of both sexes for fasting and 2-h glucose and also in the 2-h levels of men in the 25- to 34-year age-group. CONCLUSIONS: This study has highlighted a high prevalence of non-insulin-dependent diabetes mellitus in South African Indians and bimodality in the plasma glucose distribution.

Adolescent↗

High risk of progression to NIDDM in South-African Indians with impaired glucose tolerance.

A four-yr prospective study was undertaken to examine the natural history of IGT in 128 South-African Indians classified as such at year 0 of the study, based on WHO criteria. Subjects were reexamined at year 1 and year 4. Of the 113 subjects who completed the study, 50.4% progressed to NIDDM (rate of progression 12.6%/yr), 24.8% persisted with IGT, and 24.8%, reverted to NGT. The majority (72%) who progressed to NIDDM did so in year 1. At year 1, 47 subjects were still classified as IGT; of the 40 subjects completing the study, 16 subjects (40%) progressed to NIDDM, 17 subjects (42.5%) persisted with IGT, and 7 subjects (17.5%) reverted to NGT. Examination of risk factors predictive of subsequent progression to NIDDM was undertaken by analysis of baseline variables in two ways: When year 0 was used as baseline (in 113 IGT0 subjects), significant predictive risk factors were the FPG and 2-h plasma glucose concentrations. All subjects who at year 0 had 2-h plasma glucose > or = 10.2 and < 11.1 mM or FPG > or = 7.3 but < 7.8 mM, subsequently progressed to NIDDM. When year 1 was used as baseline (40 IGT1 subjects), 90-min plasma glucose concentration (midtest level) was found to be a significant risk factor for development of NIDDM. In conclusion, this study has demonstrated that in South-African Indians with IGT, the majority (50.4%) progress to NIDDM within 4 yr; significant predictors of subsequent diabetes are the baseline fasting and 2-h plasma glucose concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗