Obesity is increasing in Africa, but the underlying genetic background largely remains unknown. We assessed existing evidence on genetic determinants of obesity among populations within Africa. ...MEDLINE and EMBASE were searched and the bibliographies of retrieved articles were examined. Included studies had to report on the association of a genetic marker with obesity indices and the presence/occurrence of obesity/obesity trait. Data were extracted on study design and characteristics, genetic determinants and effect estimates of associations with obesity indices. According to this data, over 300 polymorphisms in 42 genes have been studied in various population groups within Africa mostly through the candidate gene approach. Polymorphisms in genes such as ACE, ADIPOQ, ADRB2, AGRP, AR, CAPN10, CD36, C7orf31, DRD4, FTO, MC3R, MC4R, SGIP1 and LEP were found to be associated with various measures of obesity. Of the 36 polymorphisms previously validated by genome‐wide association studies (GWAS) elsewhere, only FTO and MC4R polymorphisms showed significant associations with obesity in black South Africans, Nigerians and Ghanaians. However, these data are insufficient to establish the true nature of genetic susceptibility to obesity in populations within Africa. There has been recent progress in describing the genetic architecture of obesity among populations within Africa. This effort needs to be sustained via GWAS studies.
Aim
It is unclear whether ketosis‐prone diabetes is a specific type or a subtype of Type 2 diabetes. We aimed to describe the clinical and metabolic features of ketosis‐prone diabetes in a ...sub‐Saharan population.
Methods
We consecutively enrolled and characterized 173 people with non‐autoimmune diabetes admitted for hyperglycaemic crisis at the Yaoundé Central Hospital, Cameroon. Blood samples were collected for fasting glucose, HbA1c, lipid profile and C‐peptide assays with insulin resistance and secretion estimation by homeostasis model assessment. People were classified as having Type 2 diabetes (n = 124) or ketosis‐prone diabetes (n = 49). Ketosis‐prone diabetes was sub‐classified as new‐onset ketotic phase (n = 34) or non‐ketotic phase (n = 15).
Results
Ketosis‐prone diabetes was found in 28.3% of the hyperglycaemic crises. Age at diabetes diagnosis was comparable in Type 2 and ketosis‐prone diabetes 48 ± 14 vs 47 ± 11 years; P = 0.13 with a similar sex distribution. Overall BMI was 27.7 ± 13.4 kg/m2 and was ≥ 25 kg/m2 in 55.8% of those taking part, however, 73.5% of those with ketosis‐prone diabetes reported weight loss of > 5% at diagnosis. Blood pressure and lipid profile were comparable in both types. Ketosis‐prone diabetes in the ketotic phase was characterized by lower insulin secretion and higher serum triglycerides compared with non‐ketotic ketosis prone and Type 2 diabetes. Type 2 and ketosis prone diabetes in the non‐ketotic phase were comparable in terms of lipid profile, blood pressure, waist‐to‐hip ratio, BMI and fat mass, insulin secretion and insulin resistance indices.
Conclusions
Ketosis‐prone diabetes is likely to be a subtype of Type 2 diabetes with the potential to develop acute insulinopenic episodes.
What's new?
Although ketosis‐prone diabetes has been described in many populations, there are few reports in sub‐Saharan populations living in Africa. This article presents some epidemiological, clinical and metabolic features of ketosis‐prone diabetes in Cameroon.
Ketosis‐prone diabetes may be more frequent than expected in sub‐Saharan Africa and is comparable with Type 2 diabetes, with the exception of acute ketotic onset and relapses and transient lower insulin secretion. Ketosis‐prone diabetes is likely to be a subtype of Type 2 diabetes with the potential to develop acute insulinopenic phases at diagnosis or during unexplained ketotic relapses.
Summary
In first‐degree relatives of type 1 diabetic patients, we investigated whether diabetes risk assessment solely based on insulinoma antigen 2 (IA‐2) and zinc transporter 8 (ZnT8) antibody ...status (IA‐2A, respectively, ZnT8A) is as effective as screening for three or four autoantibodies antibodies against insulin (IAA), glutamate decarboxylase 65 kDa (GAD) glutamate decarboxylase autoantibodies (GADA) and IA‐2A with or without ZnT8A in identifying children, adolescents and adults who progress rapidly to diabetes (within 5 years). Antibodies were determined by radiobinding assays during follow‐up of 6444 siblings and offspring aged 0–39 years at inclusion and recruited consecutively by the Belgian Diabetes Registry. We identified 394 persistently IAA+, GADA+, IA‐2A+ and/or ZnT8A+ relatives (6·1%). After a median follow‐up time of 52 months, 132 relatives developed type 1 diabetes. In each age category tested (0–9, 10–19 and 20–39 years) progression to diabetes was significantly quicker in the presence of IA‐2A and/or ZnT8A than in their joint absence (P < 0·001). Progression rate was age‐independent in IA‐2A+ and/or ZnT8A+ relatives but decreased with age if only GADA and/or IAA were present (P = 0·008). In the age group mainly considered for immune interventions until now (10–39 years), screening for IA‐2A and ZnT8A alone identified 78% of the rapid progressors (versus 75% if positive for ≥ 2 antibodies among IAA, GADA, IA‐2A and ZnT8A or versus 62% without testing for ZnT8A). Screening for IA‐2A and ZnT8A alone allows identification of the majority of rapidly progressing prediabetic siblings and offspring regardless of age and is more cost‐effective to select participants for intervention trials than conventional screening.
Aim
We evaluated the performance of the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) and Cockcroft–Gault (CG) equations against creatinine ...clearance (CrCl) to estimate glomerular filtration rate (GFR) in 51 patients with Type 2 diabetes.
Methods
The CrCl value was obtained from the average of two consecutive 24‐h urine samples. Results were adjusted for body surface area using the Dubois formula. Serum creatinine was measured using the kinetic Jaffe method and was calibrated to standardized levels. Bland–Altman analysis and kappa statistic were used to examine agreement between measured and estimated GFR.
Results
Estimates of GFR from the CrCl, MDRD, CKD‐EPI and CG equations were similar (overall P = 0.298), and MDRD (r = 0.58; 95% CI: 0.36–0.74), CKD‐EPI (r = 0.55; 95% CI: 0.33–0.72) and CG (r = 0.61; 95% CI: 0.39–0.75) showed modest correlation with CrCl (all P < 0.001). Bias was −0.3 for MDRD, 1.7 for CKD‐EPI and −5.4 for CG. All three equations showed fair‐to‐moderate agreement with CrCl (kappa: 0.38–0.51). The c‐statistic for all three equations ranged between 0.75 and 0.77 with no significant difference (P = 0.639 for c‐statistic comparison).
Conclusions
The MDRD equation seems to have a modest advantage over CKD‐EPI and CG in estimating GFR and detecting impaired renal function in sub‐Saharan African patients with Type 2 diabetes. The overall relatively modest correlation with CrCl, however, suggests the need for context‐specific estimators of GFR or context adaptation of existing estimators.
What's new?
Glomerular filtration rate (GFR) equations for estimating kidney function are routinely used in sub‐Saharan Africa. There is, however, a paucity of data on the performance of these equations in patients with diabetes mellitus who are, for the most part, undiagnosed and unaware of their condition.
We investigated the performance of the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) and Cockcroft–Gault (CG) equations in patients with Type 2 diabetes.
Our results suggest that the lowest bias is observed with the MDRD formula compared with the CKD‐EPI and CG equations. However, all three equations performed similarly in predicting altered kidney function based on low GFR.
Abstract Background Management of hyperglycaemic crises requires expensive and labour-intensive procedures that are not achievable in all clinical settings. Intramuscular (IM) insulin therapy is a ...more feasible alternative, but remains insufficiently evaluated. We report here on an audit of clinical outcomes of a simple management protocol that involves IM insulin therapy, careful rehydration and inexpensive monitoring in a resource-limited setting. Methods In June 2006, we began the routine use of a protocol based on IM insulin administration, careful rehydration and affordable monitoring for the management of hyperglycaemic crises in Yaoundé Central Hospital. Clinical records of patients admitted for hyperglycaemic crises 6 months before and 6 months after introduction of the protocol were independently coded and compared for clinical outcomes, including the 48-hour death rate as a primary endpoint. Secondary endpoints were blood glucose (BG) normalization and duration of hospital stay. Results A total of 112 patients’ files fulfilled the inclusion criteria, including 57 before and 55 after the introduction of the IM protocol (intervention). Patients of the pre-intervention group were aged 56.4 ± 2.1 years versus 53.9 ± 2.3 years in the intervention group (p = 0.41), with 23% versus 40%, respectively, with newly diagnosed diabetes ( p = 0.05), and 45% versus 41%, respectively, with significant ketosis on admission ( p = 0.84). As for the primary endpoint, 15.8% of the pre-intervention group died within 48 hours of admission versus 3.6% in the intervention group ( p = 0.03). BG was normalized within 24 hours of admission in 28.1% patients of the pre-intervention group versus 90.9% of the intervention group ( p < 0.001). However, the overall duration of hospitalization was similar in both groups. Septic shock, ketosis and high serum creatinine on admission were associated with poor outcomes in both groups. Conclusion The proposed protocol using IM insulin can be safely used to treat hyperglycaemic crises, with mortality rates comparable to those in specialized centres in developed countries.
Summary
Obesity is increasing in
A
frica, but the underlying genetic background largely remains unknown. We assessed existing evidence on genetic determinants of obesity among populations within
A
...frica.
MEDLINE
and
EMBASE
were searched and the bibliographies of retrieved articles were examined. Included studies had to report on the association of a genetic marker with obesity indices and the presence/occurrence of obesity/obesity trait. Data were extracted on study design and characteristics, genetic determinants and effect estimates of associations with obesity indices. According to this data, over 300 polymorphisms in 42 genes have been studied in various population groups within
A
frica mostly through the candidate gene approach. Polymorphisms in genes such as
ACE
,
ADIPOQ
,
ADRB
2
,
AGRP
,
AR
,
CAPN
10
,
CD
36
,
C
7orf31
,
DRD
4
,
FTO
,
MC3R
,
MC4R
,
SGIP1
and
LEP
were found to be associated with various measures of obesity. Of the 36 polymorphisms previously validated by genome‐wide association studies (
GWAS
) elsewhere, only
FTO
and
MC4R
polymorphisms showed significant associations with obesity in black
S
outh
A
fricans,
N
igerians and
G
hanaians. However, these data are insufficient to establish the true nature of genetic susceptibility to obesity in populations within
A
frica. There has been recent progress in describing the genetic architecture of obesity among populations within
A
frica. This effort needs to be sustained via
GWAS
studies.
The hyperglycemic clamp test, the gold standard of beta cell function, predicts impending type 1 diabetes in islet autoantibody-positive individuals, but the latter may benefit from less invasive ...function tests such as the proinsulin:C-peptide ratio (PI:C). The present study aims to optimize precision of PI:C measurements by automating a dual-label trefoil-type time-resolved fluorescence immunoassay (TT-TRFIA), and to compare its diagnostic performance for predicting type 1 diabetes with that of clamp-derived C-peptide release.
Between-day imprecision (n = 20) and split-sample analysis (n = 95) were used to compare TT-TRFIA (AutoDelfia, Perkin-Elmer) with separate methods for proinsulin (in-house TRFIA) and C-peptide (Elecsys, Roche). High-risk multiple autoantibody-positive first-degree relatives (n = 49; age 5-39) were tested for fasting PI:C, HOMA2-IR and hyperglycemic clamp and followed for 20-57 months (interquartile range).
TT-TRFIA values for proinsulin, C-peptide and PI:C correlated significantly (r2 = 0.96-0.99; P<0.001) with results obtained with separate methods. TT-TRFIA achieved better between-day %CV for PI:C at three different levels (4.5-7.1 vs 6.7-9.5 for separate methods). In high-risk relatives fasting PI:C was significantly and inversely correlated (rs = -0.596; P<0.001) with first-phase C-peptide release during clamp (also with second phase release, only available for age 12-39 years; n = 31), but only after normalization for HOMA2-IR. In ROC- and Cox regression analysis, HOMA2-IR-corrected PI:C predicted 2-year progression to diabetes equally well as clamp-derived C-peptide release.
The reproducibility of PI:C benefits from the automated simultaneous determination of both hormones. HOMA2-IR-corrected PI:C may serve as a minimally invasive alternative to the more tedious hyperglycemic clamp test.
In a systematic review, the authors explored genetic association studies of essential hypertension in African populations. Studies reporting on the association of polymorphism(s) with hypertension in ...African populations were included. Appropriate studies were pooled using random effects model meta‐analysis, under six potential inheritance models. In all, 46 polymorphisms in 33 genes were investigated for their association with hypertension or blood pressure levels. Meta‐analysis was possible for three single nucleotide polymorphisms: rs4340, rs699, and rs5186. An association was found between rs5186, rs699, and hypertension under allele contrast and homozygous codominant models (odds ratio, 1.63 95% confidence interval, 1.04–2.54 and 4.01 95% confidence interval, 1.17–13.80 for rs5186, respectively; and 1.80 95% confidence interval, 1.13–2.87 for rs699). Findings were mostly robust in sensitivity analyses. According to the systematic review, there is currently insufficient evidence on the specific polymorphisms that pose the risk of hypertension in African populations. Large‐scale genetic studies are warranted to better understand susceptibility polymorphisms that may be specific to African populations.
Highlights • This is a first systematic review and meta-analysis of genetic studies of T2D in Africa. • Available genetic studies of T2D in Africa mostly originate in northern Africa. • The role of ...TCF7L2 and KCNQ SNPs, which showed greatest effect in Europeans and Asians respectively, is unclear in Africans according to our meta-analysis. • Larger-scale studies will help understanding the genetic mechanisms of type 2 diabetes in Africa.
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