Characteristics of people with high visit-to-visit glycaemic variability in Type 2 diabetes.

AIMS: Increased visit-to-visit glycaemic variability is independently associated with adverse outcomes in Type 2 diabetes. Our aim was to identify the patient characteristics associated with raised visit-to-visit glycaemic variability in people with Type 2 diabetes. METHODS: A case-control study was conducted to establish associations between HbA1c variability and clinical covariates in 10 130 people with Type 2 diabetes. Variability was calculated by two metrics [sd and coefficient of variation (CV)] from a minimum of four HbA1c readings obtained over a 4-year period. High and low variability groups were defined as the top and bottom tertile of the sd or CV, and used in logistic regression analyses including a number of clinical and biochemical covariates. The analyses were stratified into low mean (< 53 mmol/mol; 7%) and high mean (≥ 53 mmol/mol; 7%) HbA1c groups. RESULTS: Findings were consistent across both HbA1c groups and variability metrics. Treatment, independent of other factors, was the most strongly associated covariate for the risk of high HbA1c variability. A six-fold increased risk was observed in the low HbA1c group, between the most and least intense treatment regimens (P < 0.001). Similar findings were present in the high HbA1c group with a three-fold increase in risk (P < 0.001). In addition, male gender, younger age, reduced HDL-cholesterol and increased BMI were all found to be independently associated with raised visit-to-visit glycaemic variability. CONCLUSIONS: Intensive treatment resulting in low mean HbA1c was associated with marked increase in HbA1c variability. Irrespective of diabetes control, the greatest visit-to-visit variability was observed in young, insulin resistant men.

Adherence in patients transferred from immediate release metformin to a sustained release formulation: a population-based study.

AIM: Metformin is the most commonly prescribed oral agent used in the treatment of type 2 diabetes. It is effective at reducing glycosylated Haemoglobin (HbA1c) and decreasing microvascular and macrovascular disease. However, up to 25% of patients develop gastrointestinal side effects leading to cessation in 5-10% of users. Metformin XL (glucophage SR) is a once a day preparation that delays absorption, leading to decreased peak metformin concentrations. We hypothesised that the XL preparation of metformin would be better tolerated than the standard immediate release (IR) preparation leading to improved adherence to therapy. METHODS: In a retrospective observational study, we studied adherence and glycaemic control in patients prescribed metformin IR and XL preparations in Tayside, UK. RESULTS: Metformin XL was used by 137 patients during the study period. Overall adherence was greater in the XL group (80%) compared with the 10,772 patients in the IR group (72%, p = 0.0026). In the 40 patients who changed from metformin IR to metformin XL who had sufficient data to determine adherence, the adherence increased from 62% in the IR group to 81% in the XL group (p < 0.0001). This was associated with an HbA1c reduction from 9.1 to 8.4% (p = 0.0739, n = 29). CONCLUSIONS: Metformin XL use is associated with increased adherence compared with the IR preparation, although the mechanism for this cannot be determined from this study. In patients intolerant of metformin IR the XL preparation should be considered.

Long-term adherence to statin treatment in diabetes.

AIMS: To determine the patterns and predictors of long-term adherence to statin therapy in all patients with diabetes in the community setting. METHODS: We retrospectively studied patients with diabetes who were resident in Tayside, Scotland from 1 January 1989 to 31 May 2003 and initiated statin treatment during that time. The main outcome measure was percentage of days covered (PDC) by a statin, calculated at regular intervals. Predictors of suboptimal adherence (PDC < 80%) were identified using generalized linear models for repeated measures. RESULTS: Six thousand four hundred and sixty-two patients were included in the study. In the first year, the mean PDC was 87, 61% in the first and second quarter, respectively, and 65% after 13 years. Less than 50% of patients maintained a PDC of > 80% after 13 years. Predictors of poor long-term adherence were younger age, higher HbA(1c), no history of smoking, no cardiovascular morbidity at baseline and occurrence of cardiovascular disease after statin commencement. CONCLUSIONS: This study suggests that barriers to long-term adherence to statins tend to arise early on in the therapeutic course. In general, long-term adherence is poor in patients with diabetes, especially among those with few other cardiovascular risk factors.

Orofacial cleft management by short-term surgical missions in South America: literature review.

There is a growing demand for surgical care in South America, particularly for patients with congenital orofacial clefts (OFCs). Short-term surgical missions (STSMs) have emerged as a means to deliver surgical expertise and alleviate this demand. The aim of this study was to review the quantity and quality of peer-reviewed reports on OFC repairs performed by STSMs in South America. A literature search was conducted using the PubMed, Embase, Web of Science, and SciELO databases. The search was limited to articles published in English and Spanish. Descriptive statistics were used for the data analysis. The search yielded 65 studies related to OFCs. Eight (12.3%) were selected for full-text review. Only five (7.7%) articles met the inclusion criteria. The diverse study designs and heterogeneous types of data assessment among the selected studies hindered a comparison between them. This review found a sparse number of publications pertaining to OFC missions to South America. The articles that were included demonstrated inconsistencies in reporting patient care data. There is a need for a more efficient, streamlined method of reporting humanitarian missions for OFC repairs in order for healthcare professionals to fulfill research and ethical obligations and offer the best practices in patient-centered care.

Adherence to insulin and its association with glycaemic control in patients with type 2 diabetes.

BACKGROUND: Good glycaemic control improves outcomes in patients with type 2 diabetes, but the extent to which this depends on adherence to insulin treatment is uncertain. AIM: To investigate the association between adherence to insulin and glycaemic control in insulin-treated patients with type 2 diabetes. DESIGN: Observational records-based study. METHODS: We studied all patients with type 2 diabetes who were resident in Tayside, Scotland from 1 January 1995 to 30 September 2001, and who were treated with insulin. Adherence to insulin treatment was measured as the annual number of days of insulin coverage on the recommended dose, calculated from the amount of drug dispensed at community pharmacies and the recommended dose level for each patient. The association between glycaemic control (HbA1c), and adherence was determined, as was the influence of covariates, including age, sex, duration of diabetes and number of injections per day. RESULTS: A total of 1099 people were studied: 574 (52%) males and 525 (48%) females, mean +/- SD age 62 +/- 12 years, diabetes duration 10 +/- 7 years. Median time in the study (time for which insulin was dispensed) was 1107 (range 366-2446) days. Insulin prescribed was 58.0 +/- 33.3 IU/day and insulin collected from pharmacies was 53.6 +/- 27.1 IU/day. Mean adherence to insulin was thus 70.6%+/-17.7%. Adherence to insulin (p = 0.0021), BMI (p = 0.0001) and diabetes duration (p = 0.0314) were all significant predictors of HbA1c. DISCUSSION: Adherence to insulin appears poor in these type 2 diabetes patients, and there was a significant relationship between adherence and long-term metabolic control.

A genome-wide association study suggests an association of Chr8p21.3 (GFRA2) with diabetic neuropathic pain.

BACKGROUND: Neuropathic pain, caused by a lesion or a disease affecting the somatosensory system, is one of the most common complications in diabetic patients. The purpose of this study is to identify genetic factors contributing to this type of pain in a general diabetic population. METHOD: We accessed the Genetics of Diabetes Audit and Research Tayside (GoDARTS) datasets that contain prescription information and monofilament test results for 9439 diabetic patients, among which 6927 diabetic individuals were genotyped by Affymetrix SNP6.0 or Illumina OmniExpress chips. Cases of neuropathic pain were defined as diabetic patients with a prescription history of at least one of five drugs specifically indicated for the treatment of neuropathic pain and in whom monofilament test result was positive for sensory neuropathy in at least one foot. Controls were individuals who did not have a record of receiving any opioid analgesics. Imputation of non-genotyped SNPs was performed by IMPUTE2, with reference files from 1000 Genomes Phase I datasets. RESULTS: After data cleaning and relevant exclusions, imputed genotypes of 572 diabetic neuropathic pain cases and 2491 diabetic controls were used in the Fisher's exact test. We identified a cluster in the Chr8p21.3, next to GFRA2 with a lowest p-value of 1.77 × 10(-7) at rs17428041. The narrow-sense heritability of this phenotype was 11.00%. CONCLUSION: This genome-wide association study on diabetic neuropathic pain suggests new evidence for the involvement of variants near GFRA2 with the disorder, which needs to be verified in an independent cohort and at the molecular level.

Common nonsynonymous substitutions in SLCO1B1 predispose to statin intolerance in routinely treated individuals with type 2 diabetes: a go-DARTS study.

SLCO1B1 gene variants are associated with severe statin-induced myopathy. We examined whether these variants are also associated with general statin intolerance in a large population of patients with type 2 diabetes receiving statins as part of routine clinical care. A total of 4,196 individuals were genotyped for rs4149056 (Val174Ala) and rs2306283 (Asp130Asn). Intolerance was defined by serum biochemistry and also by discontinuation, switching, or reduction in dose of the prescribed statin drug. Ala174 was associated with higher intolerance (odds ratio = 2.05, P = 0.043), whereas Asp130 was associated with lower intolerance (odds ratio = 0.71, P = 0.026). Ala174 was associated with a lower low-density lipoprotein cholesterol (LDLc) response to statins (P = 0.01) whereas 130D was associated with a greater LDLc response to statins (P = 0.048), as previously reported; however, this association was no longer present when data for statin-intolerant individuals were removed from the analysis. This study suggests that common genetic variants selected for an extreme phenotype of statin-induced myopathy also predispose to more common milder statin intolerance and may, for this reason, impact lipid-lowering efficacy.

The effect of obesity on glycaemic response to metformin or sulphonylureas in Type 2 diabetes.

AIMS: In treating Type 2 diabetes (T2DM), UK guidelines recommend metformin in obese and overweight patients, and either sulphonylureas or metformin in normal weight patients. Although other factors influence prescribing choice, a key objective in treating T2DM is to lower plasma glucose. There is little data on how glycaemic response to oral agents varies with body mass index (BMI). Therefore, we assessed current prescribing practice and effect of BMI on glycaemic response to sulphonylureas and metformin in a large population T2DM cohort. METHODS: BMI was determined in 3856 T2DM patients on sulphonylurea or metformin monotherapy in 2001-2002. Patients were identified from the Diabetes Audit and Research in Tayside, Scotland (DARTS) database. In a linear regression, the effect of BMI and other confounders on drug response was assessed in 2064 treatment-naïve patients commencing sulphonylureas or metformin between 1994 and 2002. RESULTS: In 2001-2002, metformin was more likely to be used in obese than non-obese patients: 13% normal weight, 33.6% overweight and 62.1% obese patients were treated with metformin. Glycaemic response to sulphonylureas was not influenced by BMI (P = 0.81). Metformin was more effective in lowering glucose in those with a lower BMI (r = -0.02, P = 0.02), although the clinical impact of this was small. The HbA(1c) reduction in non-obese patients was similar to that in obese patients (1.46% vs. 1.34%, P = 0.11). CONCLUSIONS: Glycaemic response to metformin in non-obese and obese patients is similar, suggesting that an individual's BMI should not influence the choice of oral agent. Given the non-glycaemia-related benefits of metformin, it should be used in more non-obese patients than is current practice in Tayside, Scotland.

Frequency and predictors of hypoglycaemia in Type 1 and insulin-treated Type 2 diabetes: a population-based study.

AIMS: To ascertain the frequency and identify predictors of self-reported hypoglycaemia in Type 1 and insulin-treated Type 2 diabetes. METHODS: A random sample of 267 people with insulin-treated diabetes were recruited from a population-based diabetes register in Tayside, Scotland. Each subject prospectively recorded the number of mild and severe hypoglycaemic episodes experienced over a 1-month period. Ordinal logistic regression was performed to identify potential predictors of hypoglycaemia. RESULTS: Five hundred and seventy-two hypoglycaemic events were reported by 155 patients. The participants with Type 1 diabetes had a total of 336 hypoglycaemic events with a rate of 42.89 events per patient per year. Of these, nine were severe hypoglycaemic events, with a rate of 1.15 events per patient per year. Participants with insulin-treated Type 2 diabetes experienced a total of 236 hypoglycaemic events with a rate of 16.37 events per patient per year. Of these, five were severe hypoglycaemic events, which would be equivalent to 0.35 events per patient per year. Predictors of hypoglycaemia in Type 1 diabetes were a history of previous hypoglycaemia (P = 0.006) and co-prescribing of any oral drug (P = 0.048). In patients with insulin-treated Type 2 diabetes, a history of previous hypoglycaemia (P < 0.0001) and duration of insulin treatment (P = 0.014) were significant predictors. CONCLUSION: The incidence of self-reported severe hypoglycaemia in insulin-treated Type 2 diabetes is lower than in Type 1 diabetes but does occur more often than previously reported and with sufficient frequency to cause significant morbidity. Duration of insulin treatment is a key predictor of hypoglycaemia in insulin-treated Type 2 diabetes.