Joint British Diabetes Societies guideline for the management of diabetic ketoacidosis.

The Joint British Diabetes Societies guidelines for the management of diabetic ketoacidosis (these do not cover Hyperosmolar Hyperglycaemic Syndrome) are available in full at: (i) http://www.diabetes.org.uk/About_us/Our_Views/Care_recommendations/The-Management-of-Diabetic-Ketoacidosis-in-Adults; (ii) http://www.diabetes.nhs.uk/publications_and_resources/reports_and_guidance; (iii) http://www.diabetologists-abcd.org.uk/JBDS_DKA_Management.pdf. This article summarizes the main changes from previous guidelines and discusses the rationale for the new recommendations. The key points are: Monitoring of the response to treatment (i) The method of choice for monitoring the response to treatment is bedside measurement of capillary blood ketones using a ketone meter. (ii) If blood ketone measurement is not available, venous pH and bicarbonate should be used in conjunction with bedside blood glucose monitoring to assess treatment response. (iii) Venous blood should be used rather than arterial (unless respiratory problems dictate otherwise) in blood gas analysers. (iv) Intermittent laboratory confirmation of pH, bicarbonate and electrolytes only. Insulin administration (i) Insulin should be infused intravenously at a weight-based fixed rate until the ketosis has resolved. (ii) When the blood glucose falls below 14 mmol/l, 10% glucose should be added to allow the fixed-rate insulin to be continued. (iii) If already taking, long-acting insulin analogues such as insulin glargine (Lantus(®), Sanofi Aventis, Guildford, Surry, UK) or insulin detemir (Levemir(®), Novo Nordisk, Crawley, West Sussex, UK.) should be continued in usual doses. Delivery of care (i) The diabetes specialist team should be involved as soon as possible. (ii) Patients should be nursed in areas where staff are experienced in the management of ketoacidosis.

Characteristics of Type 1 diabetes of over 50 years duration (the Golden Years Cohort).

BACKGROUND: Type 1 diabetes mellitus is associated with high levels of premature morbidity and mortality. Prolonged survival is possible, however, and some patients appear to be protected from the long-term complications of this condition. METHODS: Diabetes UK awards medals to patients who have had Type 1 diabetes for 50 years or more. By examining medal-holders, we have established the clinical and biochemical features of a group of 400 subjects (54% male) with Type 1 diabetes of long duration. RESULTS: Mean age of the subjects was 68.9 years and mean age-at-onset of diabetes 13.7 years. Features of long duration diabetes in this cohort include normal body mass (mean BMI 25.0 kg m-2), low insulin dose (mean 0.52 units kg-2) and greatly elevated HDL-cholesterol (mean 1.84 mmol/l). Mean HbA1c was 7.6% (normal range 3.8-5.0%) and no patient had a normal HbA1c at the time of venesection. As a group, they have long-lived parents and consume moderate amounts of alcohol. Medical contact has often been sporadic. A significant proportion (29%) were taking anti-hypertensive medication. Screening for micro- and macroalbuminuria was positive in 35.7%. CONCLUSIONS: Patients with long-duration (> 50 years) Type 1 diabetes are relatively protected from clinical diabetic nephropathy and large vessel disease; our data are consistent with protection possibly being genetically determined in part via elevated HDL-cholesterol levels. An abnormal urinary albumin/creatinine ratio is common in these patients, despite their low risk of significant renal deterioration; this may have implications for microalbuminuria screening programmes.

Prevalence of symptoms of depression and anxiety in a diabetes clinic population.

AIMS: To investigate the use of a short questionnaire to measure psychological symptoms in a busy clinic setting, and to examine the prevalence of these symptoms in adults with diabetes. The perceived need for psychological treatment services was also measured. METHODS: Adults (> 18 years) with either Type 1 or Type 2 diabetes were invited to complete a short demographic form and the Hospital Anxiety and Depression Scale (HADS) whilst waiting for their routine diabetes outpatients appointment. Complication status was measured via patients' medical records. Glycaemic control (HbA(1c)) was also recorded. RESULTS: A high response rate (96%) was achieved. Prevalence rates of psychological symptoms were high (overall 28% of study participants reported moderate-severe levels of depression or anxiety or both). Men were somewhat more likely to report moderate-severe depressive symptoms, whereas women reported more moderate-severe anxiety. A significant association between depression and poor glycaemic control was observed in the men, but not in the women. Regression analysis demonstrated that the interaction between sex and glycaemic control, HbA(1c) and sex were all significantly associated with depression and anxiety (R2 = 0.16 and 0.19, respectively). One-third of subjects reported that at the moment they would be interested in receiving counselling or psychotherapy if it was currently available at the diabetes clinic. CONCLUSIONS: This study has shown that the HADS is an appropriate questionnaire to use in a clinic setting in adults with diabetes. There may be a stronger association between glycaemic control and psychological symptomatology in men than in women. There remains a significant proportion of individuals with diabetes who require psychological support, which, if available, might help improve glycaemic control and thus overall wellbeing.

Human leucocyte antigen and insulin gene regions and nephropathy in type I diabetes.

AIMS/HYPOTHESIS: Diabetic nephropathy seems to have a strong genetic component. Genes involved in the genetic susceptibility to Type I (insulin-dependent) diabetes have been suggested to have a role in the development of diabetic nephropathy. This study aimed to examine the role of human leucocyte antigen and insulin genes in susceptibility to nephropathy in patients with Type I diabetes. METHODS: We carried out a genetic association study examining insulin gene polymorphisms using three large cohorts of patients with Type I diabetes: nephropathy (n = 258), long duration non-nephropathy (n = 153) and a recently diagnosed (sporadic) diabetic cohort (n = 264). Human leucocyte antigen typing results were obtained in a smaller number due to assay failures (n = 182, 126 and 200 respectively). RESULTS: No significant difference was seen in the distribution of human leucocyte antigen A, B, C, DR, DQA1 and DQB1 haplotypes and alleles between the three diabetic cohorts. No significant difference was seen in insulin '+' and '-' genotypes and alleles between the three diabetic cohorts. CONCLUSIONS/INTERPRETATION: Human leucocyte antigen and insulin gene loci are unlikely to have a major role in the susceptibility to nephropathy in Caucasian patients with Type I diabetes in the United Kingdom.

Association between stress and glycemic control in adults with type 1 (insulin-dependent) diabetes.

OBJECTIVE: To examine the relationship between stressful life events and alterations in glycemic control in adults with diabetes. RESEARCH DESIGN AND METHODS: The occurrence of stressful experiences was recorded using the life Events and Difficulties Schedule of Brown and Harris in 55 adults with type 1 diabetes. The two most recent measures of glycemic control (HbA1c) were obtained from medical records, with poor glycemic control defined by the sample median (> or =7.7%). RESULTS: Subjects whose control deteriorated over time or who remained in poor glycemic control were significantly more likely to report severe personal stressors (SPS) in the month before HbA1c measurement, compared with subjects whose control remained fair or whose control improved (43 and 25% vs. 7 and 0%; P = 0.000). Subjects whose control remained fair or whose control improved were significantly more likely to report only positive life events during the same time period (80 and 11% vs. 0 and 0%, respectively; P = 0.000). Multiple regression analysis demonstrated that SPS, sex, and lack of further education were all significantly associated with either remaining in poor control or deterioration of control. CONCLUSIONS: The study has shown that recent severe stressors are associated with poorer glycemic control. Positive life events were associated with fair or improved glycemic control. This study has its limitations, and future studies should be prospective in design. While it is not always possible to avoid stress, learning to recognize and cope with stressors may help individuals with diabetes maintain good glycemic control and improve overall quality of life.

Comparison of secondary prevention measures after myocardial infarction in subjects with and without diabetes mellitus.

OBJECTIVES: To survey and compare secondary prevention measures in diabetic and non-diabetic patients following myocardial infarction (MI). DESIGN: Follow-up of a cohort of patients who suffered their first MI 1 year previously. SETTING: Three district general hospitals. MAIN OUTCOME MEASURES: Review 1 year post-MI for signs of left ventricular failure (LVF), serum cholesterol, smoking status, weight, blood pressure and glycaemic control. Assessment of appropriate treatment with aspirin, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors and lipid-lowering therapy before discharge and at least 1 year post-MI. RESULTS: A total of 189 non-diabetic and 86 diabetic patients were studied. Most patients received beta-blockers and aspirin appropriately, and most gave up smoking. In non-diabetic subjects, cholesterol fell significantly (P < 0.05), as did the proportion of patients with cholesterol > 5.5 mmol L(-1) (P < 0.05), whereas cholesterol did not fall significantly in diabetic subjects, due to a lower proportion of patients being on lipid-lowering therapy (27.5 vs. 37.9%). A higher proportion of non-diabetic patients with LVF were treated with ACE inhibitors compared with diabetic subjects (73.6 vs. 61.%). Glycaemic control did not improve in the diabetic subjects. CONCLUSIONS: Patients with diabetes do not receive optimal secondary prevention measures compared with their non-diabetic counterparts. This issue needs to be addressed by all units dealing with patients with diabetes in order to reduce the mortality and morbidity of MI in such patients.

Genetic determinants of diabetic nephropathy.

Diabetic nephropathy is the most serious complication of diabetes mellitus. Progression of the condition leads to end-stage renal failure, and other complications of diabetes are also common in this group of patients. The onset of overt albuminuria in a patient with diabetes heralds an increased risk of death, particularly from cardiovascular disease. There is considerable evidence to show that nephropathy is influenced by genetic factors. Epidemiological studies show that only a minority of patients with diabetes develop nephropathy irrespective of glycaemic control, suggesting that a subgroup of patients are at higher risk of nephropathy. Marked ethnic variation is observed, with nephropathy being more common in certain ethnic groups. Familial clustering of nephropathy is also observed. Parental history of hypertension, diabetes or cardiovascular disease appears to predispose to nephropathy in patients with diabetes. A number of methods are available to dissect polygenic disease: animal models, genetic association studies (case-control studies), affected sib-pair studies, discordant sib-pair studies and transmission distortion analysis. Most published work has been based on association studies. Association studies have shown conflicting results often due to small numbers of cases and controls, and poor phenotypic characterization. The angiotensin-converting enzyme gene insertion (I)/deletion (D) polymorphism has been studied in detail, but does not appear to be a strong risk marker for nephropathy. It does, however, appear to have a role in response to angiotensin-converting enzyme inhibition, with II homozygotes being the most responsive and DD homozygotes the least. A number of other genetic loci have also shown positive associations with nephropathy, including apolipoprotein E, heparan sulphate and aldose reductase. More recently, affected sib-pair analysis and discordant sib-pair analysis have suggested possible genetic loci on chromosomes 3, 7, 9, 12 and 20. These have yet to be reproduced in larger numbers of families, and the specific gene regions on these chromosomes remain elusive. The evidence presented in this review strongly supports the role of genetic factors in nephropathy. Detection of strong genetic risk markers for nephropathy will allow further insights into the pathogenesis of nephropathy, and possibly the development of novel therapeutic agents for its treatment. It will also allow preventive therapy to be directed at those patients with the greatest risk for development of diabetic nephropathy.

Glomerular filtration rate determination in diabetic patients using iohexol clearance--comparison of single and multiple plasma sampling methods.

Use of iohexol clearance has been described as the gold standard for the measurement of glomerular filtration rate (GFR). It is suggested that multiple plasma sampling following iohexol injection is required to accurately determine GFR by area under plasma clearance curve. The aim of this study was to determine whether single plasma sampling 4 h after injection of iohexol could accurately determine GFR in diabetic patients with mild to moderate renal failure, compared to multiple plasma sampling. A total of 120 GFR determinations in 36 patients with non-insulin dependent diabetic renal disease were done over 1 year. No acute deterioration was seen in renal function following injection of contrast in any patient. Strong correlation in GFR measurement was observed between the multiple plasma sampling method and the single plasma sampling method (r2 = 0.975). Single plasma sampling 4 h after bolus injection of iohexol is a safe and accurate method of determining GFR and change in GFR in diabetic subjects with mild to moderate renal impairment.

Clinical, biochemical and immunological characteristics of relapsers and non-relapsers of thyrotoxicosis treated with anti-thyroid drugs.

OBJECTIVES: This study aims to correlate clinical, biochemical and immunological factors seen at diagnosis of thyrotoxicosis with subsequent relapse within 5 years. DESIGN: Retrospective review of case notes, and biochemical assessment at least 5 years after cessation of treatment. SETTING: A large general hospital endocrine clinic. SUBJECTS: Patients presenting with a first episode of thyrotoxicosis between 1988 and 1991 who were treated with antithyroid drugs for at least 18 months. Main outcome measures. Relapse was determined by examination of hospital records, general practice records, patient questionnaire and thyroid function tests. RESULTS: A total of 216 subjects presented for the first time with thyrotoxicosis, of whom 89 (41.2%) suffered a relapse of the disease. On univariate analysis, clinical factors associated with increased relapse include younger age at diagnosis, goitre, marked tachycardia, requirement for higher maintenance dose of carbimazole, higher FT4 levels at diagnosis and smoking. Factors not predictive of relapse include presence of thyroid eye signs, positive family history, atrial fibrillation or congestive cardiac failure, acropachy or pretibial myxoedema, and presence or absence of thyroid autoantibodies. Logistic regression analysis showed relapse was predominantly determined by an FT4 > 56.2 nmol L ', pulse rate > 110, presence of goitre and a positive smoking history (R2 = 0.36, P < 0.001). Presence of these four factors predicted relapse in 76 (85.4%) of the 89 patients who relapsed. CONCLUSIONS: Increased 'toxicity' of thyrotoxicosis, goitre and smoking are associated with relapse of thyrotoxicosis, and this may be helpful in determining which patients may be better managed with early ablative therapy.

Factors associated with clinic non-attendance in adults with type 1 diabetes mellitus.

In order to examine the causes of non-attendance in a diabetic clinic, a 1-year retrospective casenote review of 259 diabetic patients with no evidence of major complications was undertaken. Frequency of clinic attendance, clinic non-attendance, and glycaemic control (HbA1c) were recorded. In a sub-sample of 82 patients, more detailed demographic data was obtained via questionnaire. During the previous year 39% of patients had failed to attend the clinic on at least one occasion and 10% were recurrent non-attenders. Non-attenders had a significantly higher mean HbA1c compared with those who did attend (8.1 +/- 2.2 vs 7.6 +/- 1.6%; p = 0.03). They were also significantly younger (mean age 27 + 7 vs 29 +/- 9 yrs; p = 0.02) and had a significantly shorter duration of diabetes (12 +/- 8 vs 15 +/- 10 yrs; p = 0.02). Attendance did not differ according to gender or age of onset of diabetes. Sub-sample analysis showed that smokers, those with children at home, and single parents were all more likely to default from their appointments. Non-attendance is a significant problem at our diabetic clinic, however, by addressing the reasons why patients fail to attend clinic we hope to develop strategies to encourage regular attendance. This may be translated into improved glycaemic control and ultimately reduce the risk of late diabetic complications.

Lack of association of angiotensin II type 1 receptor gene polymorphism with diabetic nephropathy in insulin-dependent diabetes mellitus.

Several observations suggest that inherited factors are influential in the development of nephropathy in patients with insulin-dependent diabetes mellitus (IDDM). Genetic components of the renin angiotensin system are possible candidate genes. The aim of this study was to determine the role of the hypertension associated angiotensin II type 1 receptor (AT1R) gene A1166C polymorphism in susceptibility to nephropathy in IDDM. We examined 264 Caucasoid patients with IDDM and overt nephropathy (as defined by persistent proteinuria in the absence of other causes, hypertension and retinopathy), 136 IDDM patients with long duration of diabetes and no nephropathy (LDNN group), 200 recently diagnosed IDDM patients (Sporadic Diabetic group), and 212 non-diabetic subjects. The AT1R gene polymorphism was assessed using the polymerase chain reaction and restriction isotyping. Genotype frequencies did not differ significantly between the sporadic diabetic group and the nephropathy group (p = 0.245), nor between the long duration non-nephropathy group and the nephropathy group (p = 0.250). Allele frequencies were not significantly different between the three groups (p = 0.753). We conclude that there is no significant association between the hypertension associated AT1R gene polymorphism and diabetic nephropathy in patients with IDDM in the UK.