Review of Ongoing Activities and Challenges to Improve the Care of Patients With Type 2 Diabetes Across Africa and the Implications for the Future.

BACKGROUND: There has been an appreciable increase in the number of people in Africa with metabolic syndrome and Type 2 diabetes (T2DM) in recent years as a result of a number of factors. Factors include lifestyle changes, urbanisation, and the growing consumption of processed foods coupled with increasing levels of obesity. Currently there are 19 million adults in Africa with diabetes, mainly T2DM (95%), estimated to grow to 47 million people by 2045 unless controlled. This has a considerable impact on morbidity, mortality and costs in the region. There are a number of issues to address to reduce the impact of T2DM including improving detection rates and current access to services alongside addressing issues of adherence to prescribed medicines. There are also high rates of co-morbidities with infectious diseases such as HIV and tuberculosis in patients in Africa with T2DM that require attention. OBJECTIVE: Document ongoing activities across Africa to improve the care of patients with T2DM especially around issues of identification, access, and adherence to changing lifestyles and prescribed medicines. In addition, discussing potential ways forward to improve the care of patients with T2DM based on ongoing activities and experiences including addressing key issues associated with co-morbidities with infectious diseases. OUR APPROACH: Contextualise the findings from a wide range of publications including internet based publications of national approaches coupled with input from senior level government, academic and other professionals from across Africa to provide future guidance. ONGOING ACTIVITIES: A number of African countries are actively instigating programmes to improve the care of patients with T2DM starting with improved diagnosis. This recognises the growing burden of non-communicable diseases across Africa, which has been neglected in the past. Planned activities include programmes to improve detection rates and address key issues with diet and lifestyle changes, alongside improving monitoring of care and activities to enhance adherence to prescribed medicines. In addition, addressing potential complexities involving diabetes patients with infectious disease co-morbidities. It is too early to fully assess the impact of such activities. CONCLUSION: There are a number of ongoing activities across Africa to improve the management of patients with diabetes including co-morbidities. However, more needs to be done considering the high and growing burden of T2DM in Africa. Ongoing research will help further benefit resource allocation and subsequent care.

Causes of Death in a Contemporary Cohort of Patients With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease: Insights From the TECOS Trial.

OBJECTIVE: We evaluated the specific causes of death and their associated risk factors in a contemporary cohort of patients with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD). RESEARCH DESIGN AND METHODS: We used data from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) study (n = 14,671), a cardiovascular (CV) safety trial adding sitagliptin versus placebo to usual care in patients with type 2 diabetes and ASCVD (median follow-up 3 years). An independent committee blinded to treatment assignment adjudicated each cause of death. Cox proportional hazards models were used to identify risk factors associated with each outcome. RESULTS: A total of 1,084 deaths were adjudicated as the following: 530 CV (1.2/100 patient-years [PY], 49% of deaths), 338 non-CV (0.77/100 PY, 31% of deaths), and 216 unknown (0.49/100 PY, 20% of deaths). The most common CV death was sudden death (n = 145, 27% of CV death) followed by acute myocardial infarction (MI)/stroke (n = 113 [MI n = 48, stroke n = 65], 21% of CV death) and heart failure (HF) (n = 63, 12% of CV death). The most common non-CV death was malignancy (n = 154, 46% of non-CV death). The risk of specific CV death subcategories was lower among patients with no baseline history of HF, including sudden death (hazard ratio [HR] 0.4; P = 0.0036), MI/stroke death (HR 0.47; P = 0.049), and HF death (HR 0.29; P = 0.0057). CONCLUSIONS: In this analysis of a contemporary cohort of patients with diabetes and ASCVD, sudden death was the most common subcategory of CV death. HF prevention may represent an avenue to reduce the risk of specific CV death subcategories.

First Clinical Experience with Retrospective Flash Glucose Monitoring (FGM) Analysis in South Africa: Characterizing Glycemic Control with Ambulatory Glucose Profile.

BACKGROUND: In 2014, an innovative blinded continuous glucose monitoring system was introduced with automated ambulatory glucose profile (AGP) reporting. The clinical use and interpretation of this new technology has not previously been described. Therefore we wanted to understand its use in characterizing key factors related to glycemic control: glucose exposure, variability, and stability, and risk of hypoglycemia in clinical practice. METHODS: Clinicians representing affiliated diabetes centers throughout South Africa were trained and subsequently were given flash glucose monitoring readers and 2-week glucose sensors to use at their discretion. After patient use, sensor data were collected and uploaded for AGP reporting. RESULTS: Complete data (sensor AGP with corresponding clinical information) were obtained for 50 patients with type 1 (70%) and type 2 diabetes (30%), irrespective of therapy. Aggregated analysis of AGP data comparing patients with type 1 versus type 2 diabetes, revealed that despite similar HbA1c values between both groups (8.4 ± 2 vs 8.6 ± 1.7%, respectively), those with type 2 diabetes had lower mean glucose levels (9.2 ± 3 vs 10.3 mmol/l [166 ± 54 vs 185 mg/dl]) and lower indices of glucose variability (3.0 ± 1.5 vs 5.0 ± 1.9 mmol/l [54 ± 27 vs 90 ± 34.2 mg/dl]). This highlights key areas for future focus. CONCLUSIONS: Using AGP, the characteristics of glucose exposure, variability, stability, and hypoglycemia risk and occurrence were obtained within a short time and with minimal provider and patient input. In a survey at the time of the follow-up visit, clinicians indicated that aggregated AGP data analysis provided important new clinical information and insights.

Diabetes mellitus and hypothyroidism: Strange bedfellows or mutual companions?

Clinicians should be cognizant of the close relationship that exists between two of the most common endocrine disorders, primary hypothyroidism and diabetes mellitus. This applies to patients with both type 1 and type 2 diabetes mellitus (T1DM and T2DM respectively). However, the association is greater in T1DM, probably because of the shared autoimmune predisposition. In patients with T2DM, the relationship is somewhat weaker and the explanation less clear-cut. Factors such as dietary iodine deficiency, metformin-induced thyroid stimulating hormone suppression and poor glycemic control may all be implicated. Further translational research is required for greater clarification. Biochemical screening for abnormal thyroid function in individuals who have diabetes is warranted, particularly in females with T1DM, and therapy with L-thyroxine appropriately instituted if hypothyroidism is confirmed.

An epidemiological study to assess the prevalence of diabetic peripheral neuropathic pain among adults with diabetes attending private and institutional outpatient clinics in South Africa.

OBJECTIVE: To determine the prevalence of diabetic peripheral neuropathic pain (DPNP) among South African adults with type 1 or type 2 diabetes. METHODS: This cross-sectional study recruited patients with diabetes from 50 institutional/private clinics. DPNP was diagnosed using Douleur Neuropathique 4 (DN4) questionnaire (score ≥4). Health-related quality-of-life (HRQoL) and sleep were assessed with EQ-5D and Daily Sleep Interference Scale (DSIS), respectively. RESULTS: Prevalence of DPNP was 30.3% (n = 1046). Risk of DPNP was significantly increased in people aged 50-64 years (odds ratio [OR] 1.71, 95% confidence intervals [CI] 1.21, 2.41), with diabetes for ≥10 years (OR 1.55, 95% CI 1.15, 2.08), female patients (OR 1.58, 95% CI 1.18, 2.12), and black patients (OR 1.71, 95% CI 1.19, 2.46). Mean ± SD EQ-5D and DSIS scores were 0.84 ± 0.16 and 0.83 ± 1.90, respectively, in participants without DPNP versus 0.64 ± 0.25 and 3.62 ± 2.96, respectively, in those with DPNP. CONCLUSIONS: DPNP is widely prevalent in South Africa. Despite its negative impact on HRQoL and sleep, DPNP is inadequately treated. DN4 is an easy-to-use, validated questionnaire that can be used widely as a DPNP screening tool in clinical practice.

Why do some patients with type 1 diabetes live so long?

While the lifespan of people with type 1 diabetes has increased progressively since the advent of insulin therapy, these patients still experience premature mortality, primarily from cardiovascular disease (CVD). However, a subgroup of those with type 1 diabetes survives well into old age without significant morbidity. It is the purpose of this review to explore the factors which may help in identifying these patients. It might be expected that hyperglycaemia plays a major role in explaining the increased incidence of CVD and mortality of these individuals. However, while a number of publications have associated poor long term glycaemic control with an increase in both all-cause mortality and CVD in those with type 1 diabetes, it is apparent that good glycaemic control alone cannot explain why some patients with type 1 diabetes avoid fatal CVD events. Lipid disorders may occur in those with type 1 diabetes, but the occurrence of elevated high-density lipoprotein-cholesterol is positively associated with longevity in this population. Non-renal hypertension, by itself is a significant risk factor for CVD but if adequately treated does not appear to mitigate against longevity. However, the presence of nephropathy is a major risk factor and its absence after 15-20 years of diabetes appears to be a marker of long-term survival. One of the major factors linked with long-term survival is the absence of features of the metabolic syndrome and more specifically the presence of insulin sensitivity. Genetic factors also play a role, with a family history of longevity and an absence of type 2 diabetes and hypertension in the family being important considerations. There is thus a complex interaction between multiple risk factors in determining which patients with type 1 diabetes are likely to live into older age. However, these patients can often be identified clinically based on a combination of factors as outlined above.

A 24-week, prospective, randomized, open-label, treat-to-target pilot study of obese type 2 diabetes patients with severe insulin resistance to assess the addition of exenatide on the efficacy of u-500 regular insulin plus metformin.

OBJECTIVE: To compare the efficacy of 500 U/mL (U-500) regular insulin + metformin with U-500 regular insulin + metformin + exenatide in improving glycemic control in patients with severely insulin-resistant type 2 diabetes mellitus (T2DM). METHODS: Thirty patients with T2DM and severe insulin resistance were screened, and 28 were randomized to regular insulin U-500 + metformin or the GLP-1 analog exenatide, U-500, and metformin. Glycated hemoglobin (HbA1c) levels, body weight, and insulin doses were documented at baseline and at 3 and 6 months. The number and severity hypoglycemic episodes were noted. RESULTS: There were 7 males and 7 females in each group (U-500 + metformin and U-500 + metformin + exenatide). Overall, U-500 insulin + metformin, either alone or with the addition of exenatide, resulted in a significant improvement in HbA1c in both groups, with no significant difference between the 2 groups. There was no meaningful weight change in those utilizing exenatide. Those on U-500 insulin and metformin alone had a tendency toward some weight gain. No severe hypoglycemia occurred during the study period. Symptomatic hypoglycemia was more common in the group on exenatide, but this occurred in only 5 patients, and the clinical significance of this is uncertain. Insulin dosage changes on U-500 regular insulin were variable but tended to be lower in those subjects on exenatide. CONCLUSIONS: U-500 regular insulin + metformin is effective for the treatment of T2DM patients with severe insulin resistance. The addition of exenatide may ameliorate potential weight gain but provides no additional improvement in glycemia.

Treatment of recent-onset type 1 diabetic patients with DiaPep277: results of a double-blind, placebo-controlled, randomized phase 3 trial.

OBJECTIVE: To evaluate safety and efficacy of DiaPep277 in preserving ß-cell function in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: DIA-AID 1 is a multinational, phase 3, balanced-randomized, double-blind, placebo-controlled, parallel-group clinical study. Newly diagnosed patients (N = 457, aged 16-45 years) were randomized to subcutaneous injections of DiaPep277 or placebo quarterly for 2 years. The primary efficacy end point was the change from baseline in the area under the glucagon-stimulated C-peptide curve. Secondary end points were the change from baseline in mixed-meal stimulated C-peptide secretion and in fasting C-peptide and achieving target HbA1c ≤7% (≤53 mmol/mol). Partial remission (target HbA1c on insulin ≤0.5 units/kg/day) and hypoglycemic event rate were exploratory end points. RESULTS: DiaPep277 was safe and well tolerated. Significant preservation of C-peptide secretion was observed in the DiaPep277-treated group compared with the placebo (relative treatment effects of 23.4%, P = 0.037, and 29.2%, P = 0.011, in the modified intent-to-treat [mITT] and per-protocol [PP] populations, respectively). The mixed-meal stimulation failed to distinguish between the groups. There was a trend toward efficacy in fasting C-peptide levels, though not statistically significant. Significantly more DiaPep277-treated than placebo-treated patients maintained target HbA1c (mITT 56% versus 44%, P = 0.03; PP 60% versus 45%, P = 0.0082) and entered partial remission (mITT 38% versus 29%, P = 0.08; PP 42% versus 30%, P = 0.035). DiaPep277 treatment reduced the relative hypoglycemic event risk (mITT by 20%; PP by 28%). CONCLUSIONS: DiaPep277 safely contributes to preservation of ß-cell function and to improved glycemic control in patients with type 1 diabetes.

The effect of features of the metabolic syndrome on atherosclerotic risk in relatively long-surviving patients with type 1 diabetes.

BACKGROUND: Increasing numbers of patients with type 1 diabetes (T1DM) are developing features of the metabolic syndrome. The additional effect of this on the development of atherosclerosis, as inferred by the carotid artery intima media thickness (IMT), has not previously been assessed. The aim of this study was to assess the effect of features of the metabolic syndrome on carotid artery IMT in a cohort of long-surviving patients with T1DM. METHODS: Long-surviving patients with T1DM attending the Centre for Diabetes and Endocrinology were assessed regarding their risk factor profile. All underwent measurement of carotid artery IMT. In all, 156 patients who had T1DM for more than 18 years had their carotid artery IMT measured. All had been attending the clinic for over 10 years, and past clinical and laboratory records were available. RESULTS: A total of 37 patients had metabolic syndrome according to the International Diabetes Federation (IDF) definition. Those with metabolic syndrome had a significantly increased carotid artery IMT (P = 0.003) compared to those without the syndrome. There was a significant relationship between the number of features of metabolic syndrome and increased atherosclerotic risk according to the carotid artery IMT (P = 0.01). A significant correlation was found between carotid artery IMT and both waist circumference (P < 0.001) and insulin resistance (P = 0.005). CONCLUSIONS: In long-surviving patients with T1DM, those that develop metabolic syndrome are more likely to have thicker carotid artery IMT, and, by inference, be at higher risk of atherosclerosis and possibly cardiovascular disease. A linear relationship was present between both waist circumference and insulin resistance and carotid artery IMT.

Carotid artery intima-media complex thickening in patients with relatively long-surviving type 1 diabetes mellitus.

OBJECTIVE: The factors responsible for premature coronary atherosclerosis in patients with type 1 diabetes are ill defined. We therefore assessed carotid intima-media complex thickness (IMT) in relatively long-surviving patients with type 1 diabetes as a marker of atherosclerosis and correlated this with traditional risk factors. DESIGN: Cross-sectional study of 148 patients with relatively long-surviving (>18 years) type 1 diabetes (76 men and 72 women) attending the Centre for Diabetes and Endocrinology, Johannesburg. METHODS: The mean common carotid artery IMT and presence or absence of plaque was evaluated by high-resolution B-mode ultrasound. Their median age was 48 years and duration of diabetes 26 years (range 18-59 years). Traditional risk factors (age, duration of diabetes, glycemic control, hypertension, smoking and lipoprotein concentrations) were recorded. Three response variables were defined and modeled. Standard multiple regression was used for a continuous IMT variable, logistic regression for the presence/absence of plaque and ordinal logistic regression to model three categories of "risk." RESULTS: The median common carotid IMT was 0.62 mm (range 0.44-1.23 mm) with plaque detected in 28 cases. The multiple regression model found significant associations between IMT and current age (P=.001), duration of diabetes (P=.033), BMI (P=.008) and diagnosed hypertension (P=.046) with HDL showing a protective effect (P=.022). Current age (P=.001) and diagnosed hypertension (P=.004), smoking (P=.008) and retinopathy (P=.033) were significant in the logistic regression model. Current age was also significant in the ordinal logistic regression model (P<.001), as was total cholesterol/HDL ratio (P<.001) and mean HbA(1c) concentration (P=.073). CONCLUSIONS: The major factors influencing common carotid IMT in patients with relatively long-surviving type 1 diabetes are age, duration of diabetes, existing hypertension and HDL (protective) with a relatively minor role ascribed to relatively long-standing glycemic control.

Hormonal changes associated with testicular atrophy and gynaecomastia in patients with leprosy

Basal LH, FSH, 17 beta-oestradiol and testosterone and the gonadotrophin responses to luteinizing hormone releasing hormone (LHRH) were studied in male patients with leprosy (twenty-four with lepromatous and six with tuberculoid leprosy). The mean basal LH and FSH was significantly elevated in the lepromatous group and was associated with an excessive response of both gonadotrophins following LHRH administration. The mean basal testosterone and 17 beta-oestradiol values in the lepromatous group were significantly lower than those of the tuberculoid and control groups. The abnormal gonadotrophin and sex steroid values in the lepromatous group are in keeping with the testicular atrophy and gynaecomastia accompanying this form of leprosy. However, the lack of a significant correlation between basal FSH and testicular atrophy should be noted. In addition, no correlation between any of these hormonal values and gynaecomastia could be demonstrated. The patients with tuberculoid leprosy had essentially normal hormonal profiles (except for two who had raised 17 beta-oestradiol values). This is compatible with the lack of gonadal involvement in these patients.