Glucose control in Rwandan youth with type 1 diabetes following establishment of systematic, HbA1c based, care and education.

AIMS: To assess change in glycemic control concurrent with increased clinic visits, HbA1c testing, and education. Rates of complications were also examined. METHODS: A 1-2 year follow-up of 214 members of the Rwanda Life for a Child program (aged <26 years) with a first HbA1c between June 2009 and November 2010 was conducted. Data were analyzed for the entire cohort and by age (<18 years, ≥18 years). Trajectory analysis was performed to identify trends in HbA1c. RESULTS: Mean overall HbA1c decreased significantly from baseline (11.2 ± 2.7%; 99 ± 30 mmol/mol) to one- (10.2 ± 2.6%; 88 ± 28 mmol/mol) and two- (9.8 ± 26%; 84 ± 25 mmol/mol) year follow up visits. The prevalence of microalbuminuria did not significantly change (21.0%, 18.8%, and 19.6%), nor did nephropathy (4.7%, 7.8%, and 5.4%). However, rates of hypertension (31.8%, 44.9%, and 40.3%) were higher than expected. Five HbA1c groups were identified by trajectory analysis, and those with the worst control monitored their glucose significantly fewer times per week. CONCLUSIONS: The establishment of regular care, HbA1c testing, and increased education is associated with significant improvements in glycemic control in youth with type 1 diabetes (T1D) in sub-Saharan Africa, but the high prevalence of hypertension is of concern.

Current clinical status, glucose control, and complication rates of children and youth with type 1 diabetes in Rwanda.

OBJECTIVE: To describe the clinical status of youth and adolescents (≤ 25 yr) in the Rwanda Life For A Child (LFAC) program who had their first HbA1c measure in 2009 or 2010, and to identify factors which may relate to glycemic control (HbA1c) and complication status. RESEARCH DESIGN AND METHODS: Data were collected from June 2009 to November 2010 for the LFAC program in Rwanda and comprise clinical data from when participants' first HbA1c reading was obtained. RESULTS: From June 2009 to November 2010, 286 youth aged ≤25 yr had their first HbA1c. Mean age, duration, and age at diagnosis were 18.6 ± 4.5 yr, 3.4 ± 3.1 yr and 15.1 ± 4.8 yr, respectively. Mean HbA1c was 11.2 ± 2.7% with 15.7% (n = 45) having HbA1c <8%, while 30.8% (n = 88) had HbA1c >14%. Five (2.1%) had either abnormal tuning fork vibratory sensation or monofilament response, 21% (n = 31) had microalbuminuria (MA, A/C ratio >30 mg/g) and 5% (n = 7) had nephropathy (A/C ratio >300 mg/g). Diabetes duration and insulin dose/kg were positively associated with higher HbA1c, while residing in the southern province was associated with lower HbA1c. Duration, diastolic blood pressure, and HbA1c were positively associated with developing MA, while age was protective. CONCLUSIONS: These data from the LFAC program for 2009-2010 show that there is a urgent need for dramatically improved care, as many patients have greatly elevated HbA1c measures, often >14%. We have identified correlates of better control (e.g., living in the Southern province) and MA (e.g., diastolic blood pressure), which provide potential avenues to improved quality of care.

Pulse wave analysis and cardiac autonomic neuropathy in type 1 diabetes: a report from the Pittsburgh Epidemiology of Diabetes Complications Study.

BACKGROUND: The cross-sectional associations of cardiac autonomic neuropathy (CAN) with pulse wave analysis (PWA) measures (both arterial stiffness and myocardial perfusion) have not been explored in type 1 diabetes, despite recognition of an association of CAN with coronary artery disease. METHODS: Both CAN and PWA measures were obtained from 144 participants of the Pittsburgh Epidemiology of Diabetes Complications Study of childhood-onset type 1 diabetes at the 18-year follow-up examination. CAN was measured as variability in the R-R interval during deep breathing, and PWA was performed using SphgymoCor Px (AtCor Medical, Sydney, Australia). Other clinical and demographic factors were also assessed. Univariate and multivariable analyses for associations with CAN were performed for arterial stiffness measures (augmentation index [AIx] and augmentation pressure [AP]) and a myocardial perfusion measure (subendocardial viability ratio [SEVR]). RESULTS: Presence of CAN was univariately associated with all three PWA measures: AIx (odds ratio [OR]=1.5, P=0.03), AP (OR=2.1, P=0.001), and SEVR (OR=0.4, P<0.001). These relationships persisted after adjustment for potential PWA confounders. Adjusting for age and diabetes-related factors (glycosylated hemoglobin, systolic blood pressure, and overt nephropathy), CAN only remained significantly associated with SEVR (OR=0.3, P=0.005). CONCLUSIONS: CAN is cross-sectionally associated with measures of both increased arterial stiffness and decreased myocardial perfusion in type 1 diabetes; however, only the association with decreased estimated myocardial perfusion persisted in fully adjusted models. These results provide potential insight into the CAN association with coronary artery disease.

The PAM-1 aminopeptidase regulates centrosome positioning to ensure anterior-posterior axis specification in one-cell C. elegans embryos.

In the one-cell Caenorhabditis elegans embryo, the anterior-posterior (A-P) axis is established when the sperm donated centrosome contacts the posterior cortex. While this contact appears to be essential for axis polarization, little is known about the mechanisms governing centrosome positioning during this process. pam-1 encodes a puromycin sensitive aminopeptidase that regulates centrosome positioning in the early embryo. Previously we showed that pam-1 mutants fail to polarize the A-P axis. Here we show that PAM-1 can be found in mature sperm and in cytoplasm throughout early embryogenesis where it concentrates around mitotic centrosomes and chromosomes. We provide further evidence that PAM-1 acts early in the polarization process by showing that PAR-1 and PAR-6 do not localize appropriately in pam-1 mutants. Additionally, we tested the hypothesis that PAM-1's role in polarity establishment is to ensure centrosome contact with the posterior cortex. We inactivated the microtubule motor dynein, DHC-1, in pam-1 mutants, in an attempt to prevent centrosome movement from the cortex and restore anterior-posterior polarity. When this was done, the aberrant centrosome movements of pam-1 mutants were not observed and anterior-posterior polarity was properly established, with proper localization of cortical and cytoplasmic determinants. We conclude that PAM-1's role in axis polarization is to prevent premature movement of the centrosome from the posterior cortex, ensuring proper axis establishment in the embryo.