Le GLP-1 : de la physiologie À l’application thérapeutique

GLP-1 is an incretin that plays a major role in controlling glucose homeostasis in physiological state. During type 2 diabetes, its secretion is altered whereas its action isn’t, making GLP-1 a drug of choice for the treatment of the disease. However, pharmacokinetic limitations due to its enzymatic degradation by the DPP-IV have fostered the development of drugs including injectable analogues that are resistant to the action of the enzyme, and orally bioavailable DPP-IV inhibitors. Available data confirm their promising effects with a substantial advantage of analogues for their weight-reducing capacity, whereas DPP-IV inhibitors exhibit a better tolerance profile. Furthermore their combination with usual antidiabetic drugs seems beneficial, even when patients are not controlled anymore by the later. However, issues regarding the efficacy and especially the long term tolerance of these new drugs are still raised, and therefore their ultimate role in the therapeutic strategy of type 2 diabetes is still to be defined.     

Hypertension in people with diabetes in sub-Saharan Africa: revealing the hidden face of the iceberg

AIM: To evaluate the prevalence, awareness, treatment and control of hypertension in a diabetic population of Cameroon, a sub-Saharan African country. METHODS: Two hundreds and ten diabetic patients were consecutively enrolled over a 6-month period. A questionnaire was administered and physical examination done. The JNC VI and the latest WHO criteria were used to diagnose hypertension and diabetes, respectively, and control of hypertension was assessed against five different targets. RESULTS: Ninety-one percent of the participants had type 2 diabetes. Prevalence and awareness rates for hypertension were 66.7% (n=140) and 87.1% (n=122), respectively. Treatment rate among those aware of their hypertension status was 80.3% (n=98). Patients with hypertension were older, more overweight/obese and had a longer duration of diabetes. ACE inhibitors and diuretics were the two most used blood pressure (BP) lowering drugs. Following the ADA/JNC 7 goal, the control rate of hypertension among treated patients was 10.2% (n=10). CONCLUSION: Diabetic patients in Cameroon exhibit a very high prevalence of hypertension and are about three times more affected than the general population. Awareness and treatment rates are high, but the control rate is very low. Large scale studies with intervention component are urgently required.     

Prevalence and determinants of undiagnosed diabetes in an urban sub-Saharan African population

AimsTo report the prevalence of undiagnosed diabetes and its determinants among adults Cameroonian urban dwellers.MethodsOn May 17th 2011, a community-based combined screening for diabetes and hypertension was conducted simultaneously in four major Cameroonian cities. Adult participants were invited through mass media. Fasting blood glucose was measured in capillary blood.ResultsOf the 2120 respondents, 1591 (52% being men) received a fasting glucose test. The median age was 43.7 years, and 64.2% were overweight or obese. The sex-specific age adjusted prevalence (for men and women) were 10.1% (95% confidence interval [CI]: 8.1–12.1%) and 11.2% (95%CI: 9.1–13.3%) for any diabetes, and 4.6% (95%CI: 2.6–6.6%) and 5.1% (95%CI: 3.0–7.2%) for screened-detected diabetes, respectively. The prevalence of diabetes increased with increasing age in men and women (all p ≤ 0.001 for linear trend). Older age (p < 0.001), region of residence (p < 0.001), excessive alcohol intake (p = 0.02) were significantly associated with screened-detected diabetes, while physical inactivity, body mass index, and high waist girth were not significantly associated with the same outcome.ConclusionsPrevalence of undiagnosed diabetes is very high among Cameroonian urban dwellers, indicating a potentially huge impact of screening for diabetes, thus the need for more proactive policies of early detection of the disease.     

Blood pressure variables and prevalent electrocardiographic left ventricular hypertrophy in sub‐Saharan African individuals with type 2 diabetes

Background: The aim of the present study was to investigate whether brachial blood pressure (BP) variables (systolic BP [SBP], diastolic BP [DBP], pulse [PP] and mean arterial pressure [MAP]) are similar determinants of prevalent electrocardiographic left ventricular hypertrophy (LVH) in sub‐Saharan Africans with type 2 diabetes (T2D). Methods: The study included 420 individuals (49% men) with T2D who were receiving chronic care in two main referral centers in the two major cities (Douala and Yaounde) of Cameroon. Logistic regression models were used to estimate the odds ratio (OR) and 95% confidence intervals (CI) for a standard deviation (SD) higher level of SBP (25 mmHg), DBP (13), PP (18) and MAP (20) with the risk of LVH. Discrimination was assessed and compared with c‐statistics and relative integrated discrimination improvement (RIDI; %). Results: The multivariable adjusted OR (95% CI) for prevalent LVH with each SD higher pressure variable was 1.61 (1.22–2.11) for SBP, 1.27 (0.99–1.63) for DBP, 1.62 (1.23–2.15) for PP and 1.44 (1.11–1.87) for MAP. Comparison of c‐statistics revealed no difference in the discrimination power of models with each of the BP variables (P > 0.09). However, RIDI showed enhanced discrimination in the models when other BP variables were replaced with PP. However, this enhancement was marginal for SBP. Using BP combinations modestly improved discrimination. Conclusions: The best predictors of prevalent LVH in the present study population were PP and SBP, whereas DBP was the least effective predictor. These findings have implications for cardiovascular risk stratification and monitoring of risk‐reducing therapies.     

β- and α-Cell Dysfunctions in Africans With Ketosis-Prone Atypical Diabetes During Near-Normoglycemic Remission

OBJECTIVE

Ketosis-prone atypical diabetes (KPD) is a subtype of diabetes in which the pathophysiology is yet to be unraveled. The aim of this study was to characterize β- and α-cell functions in Africans with KPD during remission.

RESEARCH DESIGN AND METHODS

We characterized β- and α-cell functions in Africans with KPD during remission. The cohort comprised 15 sub-Saharan Africans who had been insulin-free for a median of 6 months. Patients in remission were in good glycemic control (near-normoglycemic) and compared with 15 nondiabetic control subjects matched for age, sex, ethnicity, and BMI. Plasma insulin, C-peptide, and glucagon concentrations were measured in response to oral and intravenous glucose and to combined intravenous arginine and glucose. Early insulin secretion was measured during a 75-g oral glucose tolerance test. Insulin secretion rate and glucagon were assessed in response to intravenous glucose ramping.

RESULTS

Early insulin secretion and maximal insulin secretion rate were lower in patients compared with control participants. In response to combined arginine and glucose stimulation, maximal insulin response was reduced. Glucagon suppression was also decreased in response to oral and intravenous glucose but not in response to arginine and insulin.

CONCLUSIONS

Patients with KPD in protracted near-normoglycemic remission have impaired insulin response to oral and intravenous glucose and to arginine, as well as impaired glucagon suppression. Our results suggest that β- and α-cell dysfunctions both contribute to the pathophysiology of KPD.Ketosis-prone atypical diabetes (KPD) is a frequent specific subtype of diabetes in African Americans and sub-Saharan Africans (1–3). Patients with KPD present at onset with acute hyperglycemia and ketosis or ketoacidosis owing to an insulin secretory deficiency, but autoimmune markers against islet β-cells are absent (4–6). A prolonged insulin-free near-normoglycemic remission phase frequently follows the acute phase after insulin treatment and is associated with a significant recovery of the insulin secretory function (4,7,8). These observations have suggested that the blunting in insulin secretion at disease onset may be due to a functional disorder of β-cells rather than to cell destruction. We previously hypothesized that KPD is a subtype of type 2 diabetes with acute onset at diagnosis as the result of an environmental triggering factor, such as a viral infection, that severely impairs glucose-stimulated insulin secretion and favors ketogenesis (9). KPD patients display insulin resistance at the level of muscles, liver, and adipose tissue during remission (10). However, maximal insulin secretory capacity and surrogates of α-cell mass have not been evaluated, and whether α-cell dysfunction also contributes to the pathophysiology of KPD, as described in type 2 diabetes (11–14) is not known.In the current study, we therefore measured early insulin secretion in response to oral glucose, dose-response insulin secretion to intravenous glucose, and maximum secretory response to arginine combined with glucose (glucose potentiation of arginine-induced insulin secretion) in Africans with KPD during near-normoglycemic remission compared with control subjects of the same ethnic background. Function of α-cells was assessed by measuring glucagon in response to glucose, insulin, and arginine.     

How do different GLP-1 mimetics differ in their actions?

Glucagon-like peptide-1 (GLP-1) mimetics have been developed to overcome the pharmacokinetic limitations of GLP-1 for the treatment of type 2 diabetes. Their mechanisms of action and clinical effects appear particularly interesting because they target the main pathophysiologic mechanisms involved in type 2 diabetes. GLP-1 receptor agonists are more powerful and are particularly advantageous by their weight loss-inducing capacity, whereas dipeptidyl peptidase IV inhibitors exhibit a better tolerance profile. However, their ultimate role is still to be defined in the therapeutic strategy of type 2 diabetes.     

Chronic complications and quality of life of patients living with sickle cell disease and receiving care in three hospitals in Cameroon: a cross-sectional study

Background

Sickle Cell Disease (SCD) is associated with chronic multisystem complications that significantly influence the quality of life (QOL) of patients early in their life. Although sub-Saharan Africa bears 75% of the global burden of SCD, there is a paucity of data on these complications and their effects on the QOL. We aimed to record these chronic complications, to estimate the QOL, and to identify the corresponding risk factors in patients with SCD receiving care in three hospitals in Cameroon.

Methods

In this cross-sectional study, a questionnaire was used to collect data from consecutive consenting patients. Information recorded included data on the yearly frequency of painful crisis, the types of SCD, and the occurrence of chronic complications. A 36-Item Short Form (SF-36) standard questionnaire that examines the level of physical and mental well-being, was administered to all eligible participants. Data were analyzed with STATA® software.

Results

Of 175 participants included, 93 (53.1%) were female and 111 (aged ≥14 years) were eligible for QOL assessment. The median (interquartile range, IQR) age at diagnosis was 4.0 (2.0-8.0) years and the median (IQR) number of yearly painful crisis was 3.0 (1.0–7.0). The most frequent chronic complications reported were: nocturnal enuresis, chronic leg ulcers, osteomyelitis and priapism (30.9%, 24.6%, 19.4%, and 18.3% respectively). The prevalence of stroke and avascular necrosis of the hip were 8.0% and 13.1% respectively. The median (IQR) physical and mental scores were 47.3 (43.9–58.5) and 41.0 (38.8–44.6) respectively. Age and chronic complications such as stroke and avascular necrosis were independently associated with poor QOL.

Conclusions

In this population of patients living with SCD, chronic complications are frequent and their QOL is consequently poor. Our results highlight the need for national guidelines for SCD control, which should include new-born screening programs and strategies to prevent chronic complications.