Human Immunodeficiency Virus and Risk of Type 2 Diabetes in a Large Adult Cohort in Jos, Nigeria.

BACKGROUND: Human immunodeficiency virus (HIV) infection and the use of antiretroviral therapy (ART) may increase the risk of type 2 diabetes mellitus (T2DM). However, data from regions with a high burden of HIV/AIDS are limited. We determined the prevalence of T2DM at the time of presentation to a large HIV clinic in Nigeria, as well as the incidence of diabetes 12 months following ART initiation. METHODS: Data from patients enrolled for ART from 2011 to 2013 was analyzed, including 2632 patients on enrollment and 2452 reevaluated after 12 months of ART commencement. The presence of diabetes, and demographic, clinical, and biochemical data were retrieved from standardized databases. CD4(+), HIV RNA load, and hepatitis C virus status were noted. Bivariate and logistic regressions were used to identify risk factors for T2DM. RESULTS: Baseline T2DM prevalence was 2.3% (95% confidence interval, 1.8%-2.9%); age, but not body mass index (BMI), was a risk factor for diabetes. After 12 months of ART, an additional 5.3% had developed T2DM. Newly developed diabetes was not associated with age, but was associated with BMI. There were no significant associations between prevalent or incident diabetes and CD4(+), viral load, or type of ART. CONCLUSIONS: Diabetes is not uncommon in HIV-infected individuals at the time of presentation to HIV services. Patients initiating ART have a high risk of developing diabetes in the first year of ART. Excessive weight gain should be avoided, as incident diabetes was associated with a BMI ≥25.0 kg/m(2).

New susceptibility loci associated with kidney disease in type 1 diabetes.

Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS) of T1D DN comprising ~2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2 × 10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0 × 10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-ß1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1 × 10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.

Leukocytosis as an alarming sign for mortality in patients hospitalized in general wards.

There is some evidence that leukocytosis without infection is associated with increased hospital mortality, but data in this regard are very incomplete. This study was designed to investigate the relationship between leukocytosis at the time of admission and mortality among patients hospitalized in general wards. During July to Nov 2004, all deceased patients who had a white blood cell (WBC) count record for the first 24 hours of admission were selected as cases. Among survivors, twice the number of cases was selected as controls. Different levels of WBC counts were compared between cases and controls. Totally 1650 patients, including 550 deceased (cases) and 1100 survivors (controls) were analyzed. Of these, 876 (53%) were males and 774 (47%) females, and 42 (3%) were admitted to ICU, 1426 (86%) to medical and 182 (11%) to surgical wards. There was a significant difference between the mean age of deceased patients (78.0 years) and survivors (53.0 years) (P<0.0001). The median WBC for deceased and surviving patients was 9.4 and 11.4×10(9)/l, respectively. Patients with a WBC >10×10(9)/l accounted for 804, among which 335 (42%) were deceased. Leukocytosis and leukopoenia were more frequent among the deceased patients compared to the survivors. The likelihood ratio for leukocytosis and leukopenia among the cases and controls was 1.4 and 2.3, respectively. Leukocytosis was identified as an alarming sign for mortality among patients admitted to general hospital wards at early stages of admission. A quick medical intervention for amendment of the causes related to leukocytosis should consequently reduce hospital mortality.

Improving glycaemic control in African diabetic patients on insulin: a resource-free approach.

In the resource-poor areas of the tropics, diabetic patients requiring insulin are often treated with once-daily injections of intermediate-acting insulin. Glycaemic control on this regime is usually poor. We trialled a simple change to twice-daily insulin (same total daily dose, two-thirds given in morning, and one-third in evening) in a group of 20 Ethiopian diabetic patients treated in this way. Nurse support and contact, and self-glucose monitoring were not available. After three months, the haemoglobin Alc (HbAlc) had improved from 10.5 +/- 1.8 to 8.0 +/- 1.5% (P < 0.001). No improvement occurred in the 20 control patients who remained on once-daily insulin. Among the twice-daily insulin group there was a small increase in weight and mild hypoglycaemic episodes. However, all patients were very satisfied and wished to continue the new system. We conclude that a simple change from once- to twice-daily insulin, without monitoring or support, can lead to a significant improvement in the overall glycaemic control, and is suitable for resource-limited tropical countries.

Hypertension in treated and untreated patients with HIV: a study from 2011 to 2013 at the Jos University Teaching Hospital, Nigeria.

Background: Individuals with HIV, especially those on antiretroviral therapy (ART), may have increased risk of hypertension. We investigated the prevalence of hypertension at enrolment and 12 months after commencing ART in a Nigerian HIV clinic. Methods: Data from patients enrolled for ART from 2011 to 2013 were analysed, including 2310 patients at enrolment and 1524 re-evaluated after 12 months of ART. The presence of hypertension, demographic, clinical and biochemical data were retrieved from standardized databases. Bivariate and logistic regressions were used to identify baseline risk factors for hypertension. Results: Prevalence of hypertension at enrolment was 19.3% (95% CI 17.6-20.9%), and age (p<0.001), male sex (p=0.004) and body mass index (BMI) (p<0.001) were independent risk factors for hypertension. Twelve months after initiating ART, a further 31% (95% CI 17.6-20.9%) had developed hypertension. Total prevalence at that point was 50.2%. Hypertension among those on ART was associated with age (p=0.009) and BMI (p=0.008), but not with sex. There were no independently significant associations between hypertension and CD4+ counts, viral load or type of ART. Conclusions: Hypertension is common in HIV infected individuals attending the HIV clinic. Patients initiating ART have a high risk of developing hypertension in the first year of ART. Since BMI is modifiable, life-style advice aimed at weight reduction is strongly advisable.

The rising incidence of childhood type 1 diabetes and reduced contribution of high-risk HLA haplotypes.

The incidence of childhood type 1 diabetes has risen over the past 50 years. We compared the frequency of HLA class II haplotypes in 194 patients diagnosed more than 50 years ago and 582 age-matched and sex-matched individuals diagnosed between 1985 and 2002. The proportion of high-risk susceptibility genotypes was increased in the earlier cohort (p=0.003), especially in those diagnosed at age 5 years or younger, which is consistent with the hypothesis that the rise of type 1 diabetes is due to a major environmental effect.

Critical illness with hyponatraemia and impaired cell membrane integrity--the "sick cell syndrome" revisited.

OBJECTIVE: To determine whether impaired cell membrane permeability exists in critically ill patients with "sick cell" type hyponatraemia. DESIGN AND METHODS: A 36 year old male patient was identified in an intensive care unit (ICU) with liver disease and multi-organ failure. His initial serum sodium (Na) was 101 mmol/L and osmolar gap + 35 mmol/L. A flow cytometric system was used to assess lymphocyte membrane integrity using fluorescein diacetate (FDA) and propidium iodide (PI). Following this, similar studies were carried out in 17 hyponatraemic (Na < 130 mmol/L) and 19 normonatraemic (Na > 136 mmol/L) ICU patients. RESULTS: Flow cytometry in the index patient showed two clear populations of cells-one was normal (with identical characteristics to a healthy control) and the other had dysfunctional cell membrane integrity. The extended patient series, however, revealed only 2 other patients with similar flow cytometric patterns-one hyponatraemic and one normonatraemic. CONCLUSIONS: Cell membrane studies in the index patient demonstrated supportive evidence for the "sick cell syndrome" in critically ill patients. The extended series revealed that 3/37 (8%) had this abnormality, which was however not consistently associated with hyponatraemia.

Amputation and mortality in new-onset diabetic foot ulcers stratified by etiology.

OBJECTIVE: Foot ulcers and their complications are an important cause of morbidity and mortality in diabetes. The present study aims to examine the long-term outcome in terms of amputations and mortality in patients with new-onset diabetic foot ulcers in subgroups stratified by etiology. RESEARCH DESIGN AND METHODS: Patients presenting with new ulcers (duration <1 month) to a dedicated diabetic foot clinic between 1994 and 1998 were studied. Outcomes were determined until March 2000 (or death) from podiatry, hospital, and district registers. Baseline clinical examination was done to classify ulcers as neuropathic, ischemic, or neuroischemic. Five-year amputation and mortality rates were derived from Kaplan-Meier survival analysis curves. RESULTS: Of the 185 patients studied, 41% had peripheral vascular disease (PVD) and 61% had neuropathy; 45%, 16%, and 24% of patients had neuropathic, ischemic, and neuroischemic ulcers, respectively. The mean follow-up period was 34 months (range 1-65) including survivors and patients who died during the study period. Five-year amputation rates were higher for ischemic (29%) and neuroischemic (25%) than neuropathic (11%) ulcers. Five-year mortality was 45%, 18%, and 55% for neuropathic, neuroischemic, and ischemic ulcers, respectively. Mortality was higher in ischemic ulcers than neuropathic ulcers. On multivariate regression analysis, only increasing age predicted shorter survival time. CONCLUSIONS: All types of diabetic foot ulcers are associated with high morbidity and mortality. The increased mortality appears to be independent of factors increasing ulcer risk-that is, neuropathy and PVD-in patients with established foot ulcers.

Hidden diabetes in the UK: use of capture-recapture methods to estimate total prevalence of diabetes mellitus in an urban population.

An early requirement of the UK's Diabetes National Service Framework is enumeration of the total affected population. Existing estimates tend to be based on incomplete lists. In a study conducted over one year in North Liverpool, we compared crude prevalence rates for type 1 and type 2 diabetes with estimates obtained by capture-recapture (CR) analysis of multiple incomplete patient lists, to assess the extent of unascertained but diagnosed cases. Patient databases were constructed from six sources-a hospital diabetes centre; general practitioner registers; hospital admissions with a diagnosis of diabetes; a hospital diabetic retinal clinic; a research list of patients with diabetes admitted with stroke; and a local children's hospital. Log linear modelling was used to estimate missing cases, hence total prevalence. The crude prevalence of diabetes was 1.5% (95% confidence interval [CI] 1.41, 1.52), compared with a CR-adjusted rate of 3.1% (CI 3.03, 3.19). Age-banded CR-adjusted prevalence was always higher in males than in females and the difference became more pronounced with increasing age. Among males, CR-adjusted prevalence rose from 0.4% at age 10-19 years to 18.3% at 80+ years; in females the corresponding figures were 0.4% and 9.3%. The gap between crude and CR-estimated prevalence points to a rate of 'hidden diabetes' that has substantial implications for future diabetes care.

Prediction of hospital mortality from admission laboratory data and patient age: a simple model.

OBJECTIVE: To devise a simple clinical scoring system, using age of patients and laboratory data available on admission, to predict in-hospital mortality of unselected medical and surgical patients. METHODS: All patients admitted as emergencies to a large teaching hospital in Liverpool in the 5 months July-November 2004 were reviewed retrospectively, identifying all who died in hospital and controls who survived. Laboratory data available on admission were extracted to form a derivation dataset. Factors that predicted mortality were determined using logistic regression analysis and then used to construct models tested using receiver operating characteristic curves. Models were simplified to include only seven data items, with minimal loss of predictive efficiency. The simplified model was tested in a second validation dataset of all patients admitted to the same hospital in October and November 2004. RESULTS: The derivation dataset included 550 patients who died and 1100 controls. After logistic regression comparisons, 22 dummy variables were given weightings in discriminant analysis and used to create a receiver operating characteristic curve with area under the curve (AUC) of 0.884. The model was simplified to include the seven most discriminant variables, which can each be assigned scores of 2, 3 or 4 to form an index predicting outcome; a validation dataset contained 4828 patients (overall mortality 4.7%), showed this simplified scoring system accurately predicted mortality with AUC 0.848, compared with an AUC of 0.861 in a model containing all 23 original variables. CONCLUSION: A simple scoring system accurately predicts in-hospital mortality of unselected hospital patients, using age of patient and a small number of laboratory parameters available very soon after admission.

Association of the adiponectin rs266729 C>G variant and coronary heart disease in the low risk 'Golden Years' type 1 diabetes cohort.

The C-allele of rs266729 is associated with CHD, while the G-allele of rs17300539 is associated with metabolic traits. We examined these in type 1 diabetes. For rs266729, the C-allele was associated with 8-fold increase in CHD. For rs17300539, the G-allele was associated with increases in triglycerides and waist circumference.

Gastrointestinal parasites in the immunocompromised.

PURPOSE OF REVIEW: Parasites and other infections have many effects on the gastrointestinal tract of individuals who are immunocompromised. Few reviews focus on parasitic infections, which are covered here. RECENT FINDINGS: The review first examines recent advances in our understanding of the taxonomy, diagnosis and treatment of pathogens such as cryptosporidia, cyclospora, isospora and microsporidia, which are recognized causes of diarrhoea in the immunocompromised, and discusses possible links between amoebiasis and HIV. The complex interactions of both intact and abnormal immune systems with helminth infections such as hookworm and strongyloidiasis, and with trematode infections such as schistosomiasis, are receiving increasing attention. These are discussed, together with the novel concept of using live helminths to treat inflammatory bowel disease. SUMMARY: Parasitic infections remain a significant problem for immunocompromised individuals in resource-poor settings, and further work is needed to develop accessible diagnostic tests and to improve our understanding and management of their pathogenic effects. New concepts about the interactions of helminths with host immunity suggest the need for collection of further epidemiological and clinical data to unravel the complexities of such immunological interactions.