Effects of exogenous human insulin dose adjustment on body mass index in adult patients with type 1 diabetes mellitus at Kalafong Hospital, Pretoria, South Africa, 2009 - 2014.

BACKGROUND: To maintain fasting blood glucose levels within near to the normal range in type 1 diabetes mellitus (DM), frequent insulin dose adjustments may be required with short-, intermediate- and long-acting insulin formulations. Patients on human insulin generally experience weight gain over time, regardless of the level of glycaemic control achieved. OBJECTIVES: To determine the effects of human insulin, adjusted quarterly to achieve glycaemic control, on body mass index (BMI), and establish dose regimens that achieve optimal glycaemic control without increasing BMI in patients with type 1 DM at the Kalafong Diabetes Clinic in Pretoria, South Africa. METHODS: The sample size (N=211, 48.8% male) was obtained by non-probability convenience sampling of all available records of patients with type 1 DM aged ≥18 years at baseline at the clinic. The longitudinal relationships of covariates with time-varying BMI, as well as with time-varying glycated haemoglobin (HbA1c) levels, were explored using multilevel mixed-effects linear regression modelling. RESULTS: The majority of the patients (84.8%) received the twice-daily biphasic human insulin regimen and the remainder received the basal neutral protamine Hagedorn (NPH) plus prandial regular human insulin regimen. The multivariable multilevel mixed-effects linear regression model indicated that time-varying BMI was significantly positively related to time-varying twice-daily biphasic insulin dosage (ß (standard error) 0.464 (0.190), p=0.015), baseline HbA1c (0.092 (0.026), p<0.001) and baseline BMI (0.976 (0.016), p<0.001). There were significant inverse associations with the number of years spent in the study (-0.108 (0.052), p=0.038), time-varying HbA1c (-0.154 (0.031), p<0.001) and male sex (-0.783 (0.163), p<0.001). There were non-significant negative longitudinal associations of age (-0.005 (0.006), p=0.427) and current smoking status (-0.231 (0.218), p=0.290) with BMI outcomes. CONCLUSIONS: There was no evidence that optimal quarterly-prescribed daily dosage adjustments of insulin improved and maintained blood glucose control without increasing body weight. When compared with the basal NPH plus prandial insulin regimen, twice-daily biphasic insulin was associated with a statistically significant  increase in subsequent BMI. Baseline HbA1c and BMI were also significantly positively associated with time-varying BMI. However, males appeared to be at a lower risk than females of an increase in BMI during insulin therapy. A question for further research is whether the analogue insulins will be associated with the same increase in BMI, as well as the same modest improvements in HbA1c, seen in this sample.

Impact of CYP2D6 genotype on amitriptyline efficacy for the treatment of diabetic peripheral neuropathy: a pilot study.

AIM: Therapy with low-dose amitriptyline is commonly used to treat painful diabetic peripheral neuropathy. There is a knowledge gap, however, regarding the role of variable CYP2D6-mediated drug metabolism and side effects (SEs). We aimed to generate pilot data to demonstrate that SEs are more frequent in patients with variant CYP2D6 alleles. METHOD: To that end, 31 randomly recruited participants were treated with low-dose amitriptyline for painful diabetic peripheral neuropathy and their CYP2D6 gene sequenced. RESULTS: Patients with predicted normal or ultra-rapid metabolizer phenotypes presented with less SEs compared with individuals with decreased CYP2D6 activity. CONCLUSION: Hence, CYP2D6 genotype contributes to treatment outcome and may be useful for guiding drug therapy. Future investigations in a larger patient population are planned to support these preliminary findings.

Diabetes care and complications in primary care in the Tshwane district of South Africa.

AIMS: To describe the diabetic population receiving primary care from the Tshwane district public health services and to assess the quality of care of members of this population, their level of disease control and the extent of their complications. METHODS: A cluster-randomised trial was conducted in 12 primary care clinics in Tshwane district. A total of 599 diabetic patients attending these clinics for review were consecutively interviewed and clinically examined. Data on the care received was also obtained from their clinical records for the previous 12 months. Patients randomised to the active arm of the study were screened for complications. RESULTS: The mean age was 58 years and 80.5% had a body mass index (BMI) ≥25 kg/m(2). Sixty-eight percent of patients were female. Acceptable glycaemic control and LDL-cholesterol were found for only 27% and 33% of patients, respectively (HbA1c<7%; LDL<2.5 mmol/l). Despite more than 79% of patients reporting to be hypertensive, 68% of patients had a systolic blood pressure above 130 mmHg and 64% had a diastolic blood pressure above 80 mmHg. Evaluating patient records of the preceding year, screening for eye complications was only reported in 8.2%, feet complications in 6.5%, kidney complications in 21.4% and cardiovascular complications in 7.8%. The screening prevalences found were 29% for retinopathy, 22% for maculopathy, 5% for neuropathy (neurothesiometer), 7% for nephropathy (eGFR stages 3-5), 17% for possible infarction (Rose questionnaire) and 36% for severe erectile dysfunction (SHIM questionnaire). CONCLUSION: Diabetes care and screening for complications at primary care level in the Tshwane district were found to be sub-optimal. Measures should be taken to address this.

Comparison of the VersaTREK blood culture system against the Bactec9240 system in patients with suspected bloodstream infections.

BACKGROUND: To evaluate the VersaTREK (TREK Diagnostic Systems, Cleveland, Ohio) blood culture system against the Bactec9240 (BD Microbiology, Cockeysville, MD), for the recovery of bloodstream pathogens. METHODS: Venous blood from patients with suspected bacterial sepsis was evenly distributed into bottles of each system. Positive signals were recorded and bottles processed onto standard media for organism recovery. False positive signals were regarded if no organisms were seen on Gram stain and no growth was observed. RESULTS: 177 bottles were available for analysis; the Bactec9240 system yielded 43 positive, 134 negative results and no false positive signals. The VersaTREK system had 58 positive signals with 14 being false positives. CONCLUSIONS: In our setting with high background burden of immuno-compromised patients, the VersaTREK system compared favourably with the Bactec9240 in recovering blood stream aerobic and facultative anaerobic pathogens from patients with suspected bacterial sepsis. A concern is the high false positivity rate. Due to its versatility to accommodate small and large workloads as well as using smaller volumes of blood, this system may establish itself as a useful alternative for the recovery of bloodstream pathogens.

Glycaemic control improves fibrin network characteristics in type 2 diabetes - a purified fibrinogen model.

Diabetic subjects have been shown to have altered fibrin network structures. One proposed mechanism for this is non-enzymatic glycation of fibrinogen due to high blood glucose. We investigated whether glycaemic control would result in altered fibrin network structures due to decreased fibrinogen glycation. Twenty uncontrolled type 2 diabetic subjects were treated with insulin in order to achieve glycaemic control. Twenty age- and body mass index (BMI)-matched non-diabetic subjects were included as a reference group. Purified fibrinogen, isolated from plasma samples was used for analysis. There was a significant decrease in fibrinogen glycation (6.81 to 5.02 mol glucose/mol fibrinogen) with a corresponding decrease in rate of lateral aggregation (5.86 to 4.62) and increased permeability (2.45 to 2.85 x 10(-8) cm(2)) and lysis rate (3.08 to 3.27 microm/min) in the diabetic subjects after glycaemic control. These variables correlated with markers of glycaemic control. Fibrin clots of non-diabetic subjects had a significantly higher ratio of inelastic to elastic deformation than the diabetic subjects (0.10 vs. 0.09). Although there was no difference in median fiber diameter between diabetic and non-diabetic subjects, there was a small increase in the proportion of thicker fibers in the diabetic samples after glycaemic control. Results from SDS-PAGE indicated no detectable difference in factor XIIIa-crosslinking of fibrin clots between uncontrolled and controlled diabetic samples. Diabetic subjects may have altered fibrin network formation kinetics which contributes to decreased pore size and lysis rate of fibrin clots. Achievement of glycaemic control and decreased fibrinogen glycation level improves permeability and lysis rates in a purified fibrinogen model.

Glycation of fibrinogen in uncontrolled diabetic patients and the effects of glycaemic control on fibrinogen glycation.

INTRODUCTION: Evidence exists for a relationship between glycaemic control and macrovascular disease. Non-enzymatic glycation of proteins may explain this relationship in part. We investigated the effect of blood glucose control, under out-patient conditions, on fibrinogen glycation as well as the relationship between glycated fibrinogen and glycaemic control using a new sensitive method for the measurement of glycated fibrinogen. MATERIALS AND METHODS: Blood samples were taken from twenty subjects with uncontrolled Type 2 diabetes (HbA1c>7%) to determine the levels of glycation. The subjects were then treated with insulin in order to control blood glucose. Twenty age and BMI matched non-diabetic subjects were included as a reference group. RESULTS: The subjects with diabetes had significantly higher mean fibrinogen glycation at baseline than the non-diabetic subjects (7.84 vs 3.89 mol glucose/mol fibrinogen; p<0.001). After control of blood glucose, fibrinogen glycation was reduced significantly in the subjects with diabetes (7.84 to 5.24 mol glucose/mol fibrinogen; p<0.0002). The change in glycation during the intervention correlated significantly with the change in capillary glucose in the diabetic group (r=0.6, p=0.005). Fibrinogen glycation was comparable to HbA1c in predicting glycaemic control (p=0.54). Fibrinogen glycation correlated best with the average fasting capillary glucose of the preceding 5-8 days (r=0.54, p=0.014). CONCLUSION: We conclude that glucose control under out-patient conditions decreases fibrinogen glycation in subjects with Type 2 diabetes and that glycated fibrinogen compares well with HbA1c in its relation to glycaemic control.

The effect of glycaemic control on fibrin network structure of type 2 diabetic subjects.

Diabetic subjects have been shown to have altered fibrin network structures. One possible cause may be fibrinogen glycation resulting in altered structure/function properties. We investigated the effect of glucose control on fibrinogen glycation and fibrin network structure in type 2 diabetes. Blood samples were taken from twenty uncontrolled diabetic subjects at baseline to determine the levels of fibrinogen glycation and fibrin network structures. The subjects were then treated with insulin until blood glucose control was achieved before end blood samples were taken. Twenty age- and BMI-matched non-diabetic subjects were included as a reference group. The diabetic subjects had significantly higher mean fibrinogen glycation at baseline than the non-diabetic subjects (7.84 vs. 3.89 mol glucose / mol fibrinogen; p < 0.001). This was significantly reduced during the intervention (7.84 to 5.24 mol glucose / mol fibrinogen; p < 0.0002) in the diabetic group. Both groups had high mean fibrinogen concentrations (4.25 and 4.02 g/l, diabetic and non-diabetic subjects respectively). There was no difference in fibrinogen concentration, porosity, compaction and kinetics of clot formation between the diabetic subjects and non-diabetic subjects at baseline, nor were there any changes during the intervention despite the reduced fibrinogen glycation. Fibrin network characteristics correlated well with fibrinogen but not with any markers of glycaemic control. Improved glycaemic control resulted in decreased fibrinogen glycation but not fibrinogen concentration. It seems as though porosity, compaction and kinetics of clot formation are more related to fibrinogen concentration than fibrinogen glycation in this model.

The effects of social support on health, well-being and management of diabetes mellitus: a black South African perspective.

OBJECTIVES: To determine the underlying dimensions of a social support measure and investigate the effects of social support on health, well-being and management of diabetes mellitus (metabolic control and blood pressure (BP) control). DESIGN: A cross-sectional, analytical design was used with a structured questionnaire, comprising demographic characteristics, the MOS Social Support Survey scale and the health perceptions and mental health sub-scales from the SF-20. SETTING: Two outpatient diabetes mellitus clinics in Pretoria, South Africa. PARTICIPANTS: Over a three-month period, the questionnaire was administered to 263 black diabetes mellitus outpatients (174 women and 89 men), aged between 16 and 89 years. The majority of patients (91%) were diagnosed as type 2 diabetes mellitus. Only 22% of the patients had acceptable metabolic control (HbA1c < 8.0%), in comparison with 46% who had good BP control (130/85 mmHg). There were significant differences between the clinics on BP control: participants from clinic 1 had better BP control than participants from clinic 2. RESULTS: Principal components analysis, followed by an orthogonal (VARIMAX) rotational solution, resulted in two social support factors accounting for 78.9% of the variance. The first factor was labelled socio-emotional support, due to the emphasis on close caring relationships. The second factor was concerned with the more tangible aspects of social support, such as the provision of assistance. Coefficient alpha was 0.97 (socio-emotional support), 0.95 (tangible support) and 0.97 (overall social support). Patients with lower levels of social support had poorer general health and well-being than patients with higher levels of social support. Controlling for clinic, patients with controlled BP had significantly more socio-emotional and tangible support than patients with poor BP control. CONCLUSIONS: The study demonstrated that: (1) socio-emotional and tangible support were the underlying dimensions of social support; (2) socio-emotional support is an important determinant of health and well-being; and (3) social support is beneficial for one aspect of diabetes mellitus management, namely, BP control.

Interpersonal and organizational dimensions of patient satisfaction: the moderating effects of health status.

OBJECTIVES: Based on Donabedian's structure, process, and outcome model, this study was conducted to identify the underlying dimensions of patient satisfaction for diabetic patients and determine the effects of demographic characteristics and health status on these dimensions. DESIGN: A cross-sectional analytical research design was used with a questionnaire, comprising demographic characteristics, the general and mental health items from the SF-20, and a 25-item patient satisfaction scale. SETTING AND STUDY PARTICIPANTS: The questionnaire was administered to 263 South African black diabetic outpatients from the diabetic clinics at two hospitals. There were 174 females and 89 males, aged between 16 and 89 years (mean = 53.5, sd = 13.9). The average number of years of schooling was 6.3 (sd = 4.1). Main outcome measure. A reliable and valid patient satisfaction scale. RESULTS: Factor analysis was conducted on the patient satisfaction scale and two factors, accounting for 71.6% of the variance, were extracted. The major items on Factor I were support, consideration, friendliness, and encouragement, labelled the interpersonal dimension. Factor II emphasized availability of a seat and toilet in the waiting area and cleanliness, labelled the organizational dimension. The two factors had very good reliability coefficients: 0.85 (organizational) and 0.98 (interpersonal). Multi-trait scaling showed that all items exceeded the item convergent (r > 0.40) and discriminant (Z > 1.96) validity criteria. Patients in poor general health were significantly less satisfied (P = 0.007) with the organizational quality of their care than patients in good health; patients in poor mental health were significantly less satisfied (P = 0.04) with the interpersonal quality of their care than patients in good mental health. CONCLUSIONS: The findings provided support for Donabedian's model. They demonstrated that attributes of providers and settings are major components of patient satisfaction, and showed that the scale is a reliable and valid measure of patient satisfaction for this South African population.