Long-term follow-up of a randomized controlled trial of a text-message diabetes self-management support programme, SMS4BG.

AIMS: To determine the long-term effectiveness of an individually tailored text-message diabetes self-management support programme, SMS4BG, on glycaemic control at 2 years in adults with diabetes with an HbA1c concentration > 64 mmol/mol (8%). METHODS: We conducted a 2-year follow-up of a two-arm, parallel, randomized controlled trial across health services in New Zealand. Participants were English-speaking adults with type 1 or 2 diabetes and with an HbA1c >64 mmol/mol (8%). In the main trial participants randomized to the intervention group (N=183) received up to 9 months of an automated tailored text-message programme in addition to usual care. Participants in the control group (N=183) received usual care for 9 months. In this follow-up study, 293 (80%) of 366 randomized participants in the main trial were included. The primary outcome measure was change in glycaemic control (HbA1c ) from baseline to 2 years. Mixed-effect models were used to compare the group differences at 3, 6, 9 and 24 months, adjusted for baseline HbA1c and stratification factors (health district category, diabetes type and ethnicity). RESULTS: The decrease in HbA1c at 2 years was significantly greater in the intervention group [mean (sd) -10 (18) mmol/mol or -0.9 (1.6)%] compared with the control group [mean (sd) -1 (20) mmol/mol or -0.1 (1.8)%], with an adjusted mean difference of -9 mmol/mol (95% CI -14, -5) or -0.8% (95% CI -1.2, -0.4; P<0.0001). CONCLUSIONS: Improvements in glycaemic control resulting from a text-message diabetes self-management support programme were sustained at 2 years after randomization. These findings support the implementation of SMS4BG in current practice.

Does kindness matter? Self-compassion buffers the negative impact of diabetes-distress on HbA1c.

BACKGROUND: Higher self-compassion is associated with mental and physical health benefits in both healthy and chronically ill populations. The current study investigated the role of self-compassion in predicting depression, diabetes-specific distress and HbA1c in patients with diabetes. AIMS: To assess the specific operationalization of negative emotionality that best predicted HbA1c and to test whether self-compassion would buffer HbA1c in patients with diabetes against the negative effects of distress. METHODS: Patients with diabetes (n = 110) completed measures assessing trait self-compassion, depression and diabetes-distress. HbA1c results were obtained through medical records. RESULTS: As expected, diabetes-specific distress was a better predictor of HbA1c than depression; self-compassion moderated the relationship between distress and HbA1c such that higher distress predicted higher HbA1c at lower levels of self-compassion, but not at higher levels of self-compassion. CONCLUSIONS: In addition to further demonstrating the link between distress and metabolic outcomes, these findings suggest that self-compassion might buffer patients from the negative metabolic consequences of diabetes-distress.

A study of venous thrombosis incidence in patients with acute hyperthyroidism.

BACKGROUND: Hyperthyroidism is not a widely acknowledged risk factor for venous thrombosis (VT), such as deep vein thrombosis, pulmonary embolism and cerebral VT. Several case reports and case-control studies support an association between VT and hyperthyroidism. Prothrombotic changes in the coagulation pathway in thyrotoxic subjects include reversible elevation of factor VIII and von Willebrand factor, and give biological plausibility to the association and possibly causation for VT. AIM: We sought to determine the incidence of symptomatic VT in acute hyperthyroidism. METHODS: A retrospective review of consecutive outpatients presenting to the endocrinology clinic at our district hospitals from January 2006 to December 2008 with acute hyperthyroidism was carried out. All occurrences of objectively proven symptomatic VT (deep vein thrombosis, pulmonary embolism and cerebral vein thrombosis) in the 6 months following the diagnosis of hyperthyroidism were sought. RESULTS: Four hundred and twenty-eight patients were identified, of whom most were female (80%) and relatively young (mean age 47 years). Three patients (0.70%: 95% confidence interval 0.14-2.0%) were identified with a confirmed VT within 6 months of the diagnosis of hyperthyroidism. CONCLUSIONS: Although the literature suggests moderate association between VT and acute hyperthyroidism, our data show that the absolute risk is low. Furthermore, our data suggest that hyperthyroidism is usually an additional risk factor but rarely the sole risk factor for VT.

Does a diabetes annual review make a difference?

AIMS: To determine whether a diabetes annual review, independently of other care processes, is followed by improved patient clinical measurements. METHODS: Audits conducted independently of the diabetes annual review were analysed for a time-trend in patient clinical measures. An interaction variable between the review and the year of audit was used to test for a change in gradient before and after a diabetes annual review. Each patient formed their own control. RESULTS: The data included 9471 audits on 3397 patients from 92 practices, and diabetes annual reviews from 2003 to mid-2008. Percentages of patients with raised HbA(1c) , systolic blood pressure and lipids improved from first to last audit. Predicted means after a diabetes annual review for HbA(1c) decreased by 0.13% (1.0 mmol/mol), for HDL cholesterol increased by 0.04 mmol/L and for triglyceride decreased by 0.2 mmol/L. Predicted systolic and diastolic blood pressure, total cholesterol and urinary albumin:creatinine ratio did not change significantly. CONCLUSIONS: Metabolic control improved over time but this was largely independently of the diabetes annual review, which appears to add little clinical value to existing New Zealand general practice care processes. Currently, general practitioners are paid to undertake a diabetes annual review and report the measurements collected. We would argue that payment needs to be directed to demonstrating appropriate changes in clinical management or achieving meaningful clinical goals, and that the annual review results should be part of systematic feedback to general practitioners, particularly directed at clinical inertia.

Diabetes in general practice: Tongans in Tonga and South Auckland.

The aim of this study was to compare the management and treatment outcomes of Tongan diabetic patients in Tonga and South Auckland, New Zealand. This was achieved by comparison of Tongan diabetic patients within clinical audits from a general practice in Tonga (n = 124) with those from participating general practices in South Auckland (n = 168). Our results indicate that some measures of diabetes care and outcomes were similar or even better in Tonga, while some interventions were not available in Tonga. Control of weight, glucose, blood pressure and cholesterol remained difficult in both areas. Severe diabetic foot damage was more common among Tongan patients in Tonga (6.5% vs 1.8%, P < 0.05). This international comparison shows that Tongans in both Tonga and New Zealand remain at high-risk of complications independent of the health system under which care is being delivered. While barriers to implementation may differ in the two settings, improvements in the co-ordination of care are likely to be of benefit in both settings.

The Diabetes Care Support Service for general practitioners in Auckland.

AIMS: Diabetic complications can often be prevented by timely detection and intervention. Optimising diabetes care requires effective monitoring of risk factors at both practice and district level. We describe a novel method which combines district monitoring of diabetes with enhanced diabetes care by individual general practitioners. METHODS: All general practitioners in south and west Auckland (n = 291) were invited to join the Diabetes Care Support Service (DCSS). This involved the identification of all diabetic patients within the practice and the completion of an audit from with key measures of diabetes and its care. RESULTS: Audit was completed for 217 (75%) of general practitioners and 4611 diabetic patients: 39% of general practitioners completed their own audit. The proportion of completed patient assessments ranged between 35% (foot pulses) and 89% (blood pressure). The process was found to be helpful by 88% of general practitioners (who commented). CONCLUSION: The DCSS is a seamless, service-orientated approach to the delivery of diabetes care by primary and secondary services and is likely to improve care district-wide and identify the need for further interventions. Subsequent audit passes will allow the demonstration and monitoring of any changes that occur, as well as the demonstration of its feasibility and acceptability on an ongoing basis.

Influence of portal delivery of insulin on intracellular glucose and lipid metabolism.

We have investigated whether portal delivery of insulin as a result of intrahepatic islet cell autografts would prevent the development of metabolic alterations. Seven pancreatectomized dogs received islet autografts transplanted into the liver through the portal vein (PD). One year after transplantation, their intravenous glucose tolerance and insulin responses were similar to age-matched control (C) dogs (n = 5). Also, normal triglyceride content in arterial smooth muscle and striated muscle was observed in the dogs with portal insulin delivery in contrast to the substantial increases we observed in pancreatectomized dogs (n = 7) with pancreatic autografts that drained into the systemic circulation (SD). In these dogs, the tissue samples were taken at the age of 3 to 4 years. Triglyceride content (mean +/- SEM) in the aorta was 4.9 +/- 1.2 versus 2.6 +/- 0.6 versus 20.7 +/- 8.0 mumol/g (P less than .01) in C, PD, and SD models, respectively. The corresponding values for triglyceride content in striated muscles were 29.1 +/- 1.2, 25.9 +/- 1.5, and 171.4 +/- 46.6 mumol/g (P less than .01). Glucose-6-phosphate dehydrogenase (G-6-PDH) and malic enzyme, key enzymes for lipid synthesis, were also normal in the PD model, in contrast to the fivefold increased activity of these enzymes in the SD model (P less than .01). The glycolytic enzymes, hexokinase (HK) and phosphofructokinase (PFK), were normal compared with the decreased values in the SD. These data indicate that it is possible to normalize glucose and lipid metabolism in arterial walls by portal delivery of insulin, following intrahepatic islet cell transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypoglycaemia in insulin dependent diabetic patients attending an outpatients' clinic.

One hundred and fifty-eight patients with insulin dependent diabetes mellitus attending two Auckland outpatient clinics answered a questionnaire about hypoglycaemia. Almost all (98%) had experienced hypoglycaemic episodes and for 30% these were a major problem. Seventy-seven percent reported nocturnal hypoglycaemia, 39% of whom required external assistance during episodes. Forty-three percent had experienced coma, or convulsions during hypoglycaemia and a small group, 7%, had recurrent severe episodes. Twenty percent carried no diabetic identification and 13% did not routinely carry a glucose supply. Only 38% of patients kept glucagon at home. Forty percent of patients driving vehicles had experienced hypoglycaemia while driving and 13% reported traffic accidents attributed to hypoglycaemia. Hypoglycaemia is a major problem for many patients taking insulin. Improved education, wider availability of glucagon and more liberal glycaemic control of patients with problematic hypoglycaemia may be advisable.

Vitamin B12 concentrations in the elderly: a regional study.

A prospective study of 100 subjects over 70 years of age residing in rest homes or geriatric wards within the Auckland region showed that 23% of the population sampled had a serum vitamin B12 concentration below the reference range. Less than half (48%) of the group with a reduced serum vitamin B12 concentration had other haematological findings on initial screening suggestive of megaloblastosis. Comparative data from hospital and community based laboratories demonstrated that 20% and 29% respectively of samples from individuals aged greater than 70 years referred for serum vitamin B12 analysis had a B12 concentration below the reference range. Reduced serum vitamin B12 abnormalities in elderly individuals should not be ignored and some guidelines for investigations with which to establish a diagnosis are presented.

Necrobiosis lipoidica diabeticorum: a clinicopathologic study.

Necrobiosis lipoidica diabeticorum is an unusual dermatologic condition with a characteristic clinical appearance and a clear association with diabetes mellitus. There is currently no treatment that reverses the atrophic changes associated with this lesion. We have carried out a clinicopathologic study on 15 subjects and, in addition, have reviewed 10 further biopsy specimens of necrobiosis lipoidica diabeticorum. We found a frequent association of necrobiosis lipoidica diabeticorum with other chronic complications of diabetes mellitus, including limited joint mobility. It is possible that nonenzymatic glucosylation or other changes in collagen may be important in the etiology of necrobiosis lipoidica diabeticorum and the limited joint mobility. We confirmed that cutaneous anesthesia is usually present in the necrobiosis lipoidica diabeticorum lesions. With the use of an antibody to S100 protein and an immunohistochemical method, there was an apparent decreased number of nerves in the skin lesions. We suggest that sensory loss results from local destruction of cutaneous nerves by the inflammatory process. Finally, in six elliptical biopsies extending into clinically normal skin, we demonstrated that the inflammatory infiltrate of necrobiosis lipoidica diabeticorum extended from the lesion into apparently normal skin surrounding clinically active lesions. Thus, intradermal steroids might be administered to perilesional areas surrounding active lesions in the hope of halting progression.

Fructosamine in a diabetic clinic.

Serum fructosamine concentrations were measured in 660 adults attending the diabetic clinic at Auckland Hospital over a 12 month period. Only 44 (6.6%) patients had results within the physiological range whereas 237 (35.9%) patients had values greater than 3.7 mmol/l consistent with poor blood glucose control. Moreover, patients with elevated frustosamine values had a much higher frequency of retinopathy than the normal fructosamine group. When frustosamine values were compared with physician's assessment of control and with random glucose results, we found weak correlations suggesting that poor control in many patients was not previously recognised. We conclude that fructosamine measurement in a diabetic clinic provides important clinical information complementing traditional assessments of metabolic control.

Surgery for temporal lobe epilepsy.

Twenty-six patients were subjected to temporal lobectomy for complex partial seizures resistant to anticonvulsant control. The criteria for selection were simple. There should be EEG evidence of epileptiform activity arising predominantly in one temporal lobe. It was desirable that psychometric tests should confirm the localisation by showing defects of function in this lobe, and necessary that they should demonstrate normal function in the other. There should be no radiological evidence of a gross structural lesion. Twenty-four patients have been followed for 5 to 17 years, two being lost at 3 and 4 years. After operation, 50% were completely free from seizures, and in a further 38% seizures were reduced in frequency by at least 75%. There was no mortality, and the only morbidity was a minor quadrantic hemianopia, usually unnoticed by the patient. A significant improvement in mental state was noted in many patients. It is concluded that to use simple criteria for selection of patients for temporal lobectomy gives worthwhile results. There are many patients in the community who could be selected for surgery on these criteria with a high probability that their condition would be improved.

Natural history of intrahepatic canine islet cell autografts.

We have serially followed the function of intrahepatic canine islet autografts in 15 beagle dogs for up to 24 mo. Of these, only 20% sustained normal levels of fasting blood glucose for greater than 15 mo posttransplant. Failure of autograft function was accompanied by a preferential loss of well-granulated beta cells in the engrafted islets. The chronic stimulation of an initially marginal intrahepatic beta-cell mass ultimately resulted in metabolic deterioration and loss of beta cells below the minimal threshold required to maintain normal fasting blood glucose levels. It is possible that transplantation of a larger mass of islets would result in indefinite graft function in dogs. However, it remains to be demonstrated in larger mammals, including humans, whether an islet cell mass that is initially adequate in a heterotropic site such as the liver can remain functionally competent over a prolonged period.

Apolipoprotein E-containing lipoproteins and lipoprotein remnants in experimental canine diabetes.

The effects of diabetes on plasma lipoproteins were examined in a cohort of control and streptozocin-alloxan diabetic beagles fed either standard rations or an atherogenic cholesterol-supplemented diet. Lipoprotein cholesterol, triglyceride, and retinyl ester concentrations were measured in fractions separated by density gradient ultracentrifugation. Individual lipoprotein classes and apolipoproteins were assessed by electrophoresis. Postheparin plasma lipoprotein triglyceride lipase activities were also examined. In the absence of added dietary cholesterol, diabetic animals became hypercholesterolemic with relatively increased low-density (LDL) and decreased high-density (HDL) lipoprotein cholesterol concentrations. Apolipoprotein E-containing beta- to alpha 2-migrating HDL1 (HDLc) appeared in rho = 1.020-1.080 g/ml subfractions, whereas alpha 1-migrating typical HDL (rho = 1.06-1.21 g/ml) was reduced. In comparison to nondiabetic cholesterol-fed animals, diabetic cholesterol-fed animals had increased cholesterol (but not triglyceride) concentrations in very-low- and intermediate-density classes. These classes contained retinyl esters and low-molecular-weight apolipoprotein B (components of intestinal lipoprotein remnants) as well as apolipoprotein E and high-molecular-weight apolipoprotein B. These findings could not be explained by decreased postheparin plasma lipoprotein lipolytic activities. Increased plasma concentrations of HDLc in poorly controlled diabetic dogs may reflect a pathologic disturbance in the excretory limb of cholesterol transport from peripheral cells to the liver. In addition, exaggerated retention of lipoprotein remnants in cholesterol-fed diabetic dogs may contribute to increased delivery of cholesterol to extrahepatic tissues. This model appears to be suitable for physiologic studies of the effects of diabetes on reverse cholesterol transport.

The effects of hyperinsulinemia on arterial wall and peripheral muscle metabolism in dogs.

Peripheral hyperinsulinemia may be associated with metabolic consequences that could contribute to the high incidence of macrovascular disease in patients with diabetes mellitus. Arterial wall and striated muscle cells were studied in dogs to examine the effect of hyperinsulinemia on the lipid content and on lipogenic and glycolytic enzyme activity. Eight pancreatectomized dogs received segmental pancreatic autografts with venous drainage into the iliac vein. Glucose disappearance rates (K values) were normal four years after transplantation, but both fasting serum insulin levels (48.9 +/- 4.8 v 11.8 +/- 1.9 microU/mL) and the total area under the glucose-insulin response curve (1797 +/- 196 v 1110 +/- 158 microU X min/mL) were significantly greater than in control animals (P less than 0.05). The hyperinsulinemic dogs had a marked triglyceride elevation in arterial smooth muscle (20.6 +/- 8.0 v 0.5 +/- 0.4 mumol/g) and striated muscle (171.4 +/- 46.6 v 41.2 +/- 7.7 mumol/g) (P less than 0.001). Moreover, key enzymes in lipid synthesis (glucose-6-phosphate dehydrogenase, malic enzyme, and 3-hydroxyacyl-CoA DH) were significantly increased (P less than 0.01) in the hyperinsulinemic animals, while the glycolytic enzymes, (phosphofructokinase, hexokinase, pyruvate kinase, and alpha-glycerophosphate DH) were not significantly different. These data demonstrate substantial enhancement of lipid synthesis in arterial wall and striated muscle in hyperinsulinemic dogs. Altered substrate metabolism in arterial walls, in association with hyperinsulinemia, may have important implications with regard to macrovascular disease in diabetes, particularly in insulin-treated patients. In addition, these studies may serve to stimulate longer term assessments of macroangiopathy in the increasing number of patients with functioning pancreatic allografts draining into the systemic circulation.

Successful long-term survival of pancreatic islet allografts in spontaneous or pancreatectomy-induced diabetes in dogs. Cyclosporine-induced immune unresponsiveness.

Nineteen pancreatectomized beagles and three spontaneously diabetic dogs were recipients of canine islet allografts from one or more unrelated donors. The islets, enriched 30-45-fold for endocrine cells and contained in a packed cell volume of less than 1.5 ml, were engrafted in the livers of recipient animals. Treatment of diabetic recipients with cyclosporine (CsA) was begun 3-5 days before islet transplantation and the initial dosage was adjusted to attain and maintain CsA serum trough levels between 400 and 600 ng/ml. Five dogs with CsA levels less than this (155 +/- 35 SEM ng/ml) at the time of transplantation promptly rejected their grafts, whereas rejection was encountered in only 1 of 17 diabetic animals in which the initial level exceeded 400 ng/ml. CsA was discontinued 30, 60, or 90 days after continuous therapy in 10 animals. Graft failure was observed 2 mo after stopping CsA in 1 animal and 5 mo in the other. Eight other islet allograft recipients have sustained fasting euglycemia for 7 and 8 mo in 2 and for at least 2 mo in the remainder. These results demonstrate that short-term CsA therapy prolongs survival of islet allografts and induces a state of immune unresponsiveness to islet alloantigens in dogs with experimental and spontaneous diabetes. The findings are unique for a nonrodent mammal and thus hold promise that similar results may be achieved for islet allografts of other mammalian species, including humans.

Long-term follow-up of canine segmental pancreatic autografts.

The functional and morphologic characteristics of free-draining, pancreatic segmental autografts (FDPS) were studied in 8 beagle dogs that had survived longer than 4 yr. After pancreatectomy, animals received FDPS autografts of the left pancreatic limb, representing approximately one-third of the total pancreas with iliac vessel anastamoses. The grafted recipients were given pancreatic enzyme supplements (Viokase). After transplantation (tx), all 8 animals sustained fasting euglycemia with no evidence of microvascular complications. After 4 yr, IVGTT revealed K-values (%/min) that were not significantly different from age-matched controls (2.9 +/- 0.5 versus 3.7 +/- 0.6, P greater than 0.05). Mean fasting serum insulin levels were significantly greater in the tx animals (49 +/- 5 microU/ml versus 12.2 microU/ml, P less than 0.001), although the incremental response to i.v. glucose (0.5 g/kg) was less than in controls (P less than 0.05). Mean fasting plasma C-peptide levels (0.09 +/- 0.01 pmol/ml versus 0.21 +/- 0.5 pmol/ml) and peak C-peptide responses to i.v. glucose were both significantly less than in controls. Sequential pancreatic biopsies up to 2.5 yr post-tx showed atrophy of the exocrine pancreas with coalescence of islets and mild fibrosis that did not progress with time. Immunoperoxidase stains confirmed the presence of insulin, glucagon, and somatostatin within nests of islet cells. Four years after transplantation of FDPS autografts in pancreatectomized dogs, excellent function is retained. The consequences of peripheral hyperinsulinemia remain to be determined.