Fixed-dose combination therapy for type 2 diabetes: sitagliptin plus pioglitazone

Importance of the field: Type 2 diabetes is typically associated with insulin resistance and dysfunction of insulin-secreting pancreatic beta-cells. Addressing these defects often requires therapy with a combination of differently acting antidiabetic agents. A potential novel combination in development brings together the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin with the thiazolidinedione pioglitazone into a fixed-dose single-tablet combination. The former component acts mainly to increase prandial insulin secretion; the latter improves insulin sensitivity.

Effects of nateglinide on the secretion of glycated insulin and glucose tolerance in type 2 diabetes

Aims: Glycation of insulin has been demonstrated within pancreatic beta-cells and the resulting impaired bioactivity may contribute to insulin resistance in diabetes. We used a novel radioimmunoassay to evaluate the effect of nateglinide on plasma concentrations of glycated insulin and glucose tolerance in type 2 diabetes. Methods. Ten patients (5 M/5 F, age 57.8 +/- 1.9 years, HbA(1c), 7.6 +/- 0.5%,, fasting plasma glucose 9.4 +/- 1.2 mmol/l, creatinine 81.6 +/- 4.5 mumol/l) received oral nateglinide 120 mg or placebo, 10 min prior to 75 g oral glucose in a random, single blind, crossover design, 1 week apart. Blood samples were taken for glycated insulin, glucose, insulin and C-peptide over 225 min. Results: Plasma glucose and glycated insulin responses were reduced by 9% (P = 0.005) and 38% (P = 0.047), respectively, following nateglinide compared with placebo. Corresponding AUC measures for insulin and C-peptide were enhanced by 36% (P = 0.005) and 25% (P = 0.007) by nateglinide. Conclusions: Glycated insulin in type 2 diabetes is reduced in response to the insulin secretagogue nateglinide, resulting in preferential release of native insulin. Since glycated insulin exhibits impaired biological activity, reduced glycated insulin release may contribute to the anti hyperglycaemic action of nateglinide. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

Psychological adjustment to Type 2 Diabetes and relationship quality

Aims To examine the associations between psychological adjustment to Type 2 diabetes and the reported quality and type of relationships with partners. Methods All participants (n = 88) completed a number of questionnaires, including twomeasures of relationship quality: the Dyadic Adjustment Scale and the PersonalAssessment of Intimacy inRelationships Scale, theDiabetesQuality of Life Scale and the ATT-19 (which assesses personal integration of diabetes). Additionally, HbA1c levels were obtained from medical notes. Results Measures of relationship quality significantly contributed to the explanation of two outcomes: personal integration of diabetes and satisfaction with the burden of self-management behaviours. More specifically, the findings demonstrate that a specific aspect of relationship quality—intimacy in recreational activities—is positively associated with the outcomesmentioned above. Conclusions People with Type 2 diabetes who are not taking insulin, who share engagement in physical activities with their partner are more likely to be psychologically well-adjusted to their diagnosis of diabetes.

Influence of pharmaceutical care on health outcomes in patients with Type 2 diabetes mellitus

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

Analysis of the association between diabetic nephropathy and polymorphisms in the aldose reductase gene in Type 1 and Type 2 diabetes mellitus

To investigate the association between polymorphisms of the aldose reductase gene and diabetic nephropathy in both Type 1 and Type 2 diabetes mellitus, and to carry out a meta-analysis of published results.

Content validity of the Illness Perception Questionnaire-Revised for people with Type 2 Diabetes: A Think-Aloud study

Objectives: To access the cognitions of adults with type 2 diabetes whilst completing items on the Illness Perceptions Questionnaire – Revised (IPQ-R). To determine whether these cognitions are congruent with the meaning of items and subscales as interpreted by researchers and clinicians using the IPQ-R and to identify the nature and extent of problems that individuals experience when completing the IPQ-R.
Design: Participants (n=36) were recruited from a primary care diabetes clinic and a hospital diabetes clinic. They were asked to complete the IPQ-R using a ‘think-aloud’ methodology.
Main Outcome Measures: Transcripts were analysed to identify instances where participants expressed problems with item completion, or where there was inconsistency between verbal and written responses.
Results: The most problematic subscales were those of ‘personal control’ and ‘consequences’.
Conclusion: Generally, participants found the IPQ-R unproblematic. However, participants had problems with the concept of ‘cure’ and ‘symptoms’ in the context of type 2 diabetes, and with the negative phrasing used in some items. These findings have important implications for the interpretation of IPQ-R scores, particularly when the IPQ-R is used as the basis for individualised interventions among people with type 2 diabetes.

Association of retinal arteriolar dilatation with lower verbal memory::The Edinburgh Type 2 Diabetes Study

Abstract


AIMS/HYPOTHESIS:

Retinal vascular calibre changes may reflect early subclinical microvascular disease in diabetes. Because of the considerable homology between retinal and cerebral microcirculation, we examined whether retinal vascular calibre, as a proxy of cerebral microvascular disease, was associated with cognitive function in older people with type 2 diabetes.

METHODS:

A cross-sectional analysis of 954 people aged 60-75 years with type 2 diabetes from the population-based Edinburgh Type 2 Diabetes Study was performed. Participants underwent standard seven-field binocular digital retinal photography and a battery of seven cognitive function tests. The Mill Hill Vocabulary Scale was used to estimate pre-morbid cognitive ability. Retinal vascular calibre was measured from an image field with the optic disc in the centre using a validated computer-based program.

RESULTS:

After age and sex adjustment, larger retinal arteriolar and venular calibres were significantly associated with lower scores for the Wechsler Logical Memory test, with standardised regression coefficients -0.119 and -0.084, respectively (p?<?0.01), but not with other cognitive tests. There was a significant interaction between sex and retinal vascular calibre for logical memory. In male participants, the association of increased retinal arteriolar calibre with logical memory persisted (p?<?0.05) when further adjusted for vocabulary, venular calibre, depression, cardiovascular risk factors and macrovascular disease. In female participants, this association was weaker and not significant.

CONCLUSIONS/INTERPRETATION:

Retinal arteriolar dilatation was associated with poorer memory, independent of estimated prior cognitive ability in older men with type 2 diabetes. The sex interaction with stronger findings in men requires confirmation. Nevertheless, these data suggest that impaired cerebral arteriolar autoregulation in smooth muscle cells, leading to arteriolar dilatation, may be a possible pathogenic mechanism in verbal declarative memory decrements in people with diabetes.