Cardiovascular disease biomarkers are associated with declining renal function in type 2 diabetes.

AIMS/HYPOTHESIS: We investigated whether biochemical cardiovascular risk factors and/or markers of subclinical cardiovascular disease were associated with the development of reduced renal function in people with type 2 diabetes. METHODS: A cohort of 1066 Scottish men and women aged 60-74 years with type 2 diabetes from the Edinburgh Type 2 Diabetes Study were followed up for a median of 6.7 years. New-onset reduced renal function was defined as two eGFRs <60 ml-1 min-1 (1.73 m)-2 at least 3 months apart with a > 25% decline from baseline eGFR. Ankle brachial pressure index (ABI), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT) were measured at baseline. Pulse wave velocity (PWV) and carotid intima media thickness were measured 1 year into follow-up. Data were analysed using Cox proportional hazards models. RESULTS: A total of 119 participants developed reduced renal function during follow-up. ABI, PWV, NT-proBNP and hsTnT were all associated with onset of decline in renal function following adjustment for age and sex. These associations were attenuated after adjustment for additional diabetes renal disease risk factors (systolic BP, baseline eGFR, albumin:creatinine ratio and smoking pack-years), with the exception of hsTnT which remained independently associated (HR 1.51 [95% CI 1.22, 1.87]). Inclusion of hsTnT in a predictive model improved the continuous net reclassification index by 0.165 (0.008, 0.286). CONCLUSIONS/INTERPRETATION: Our findings demonstrate an association between hsTnT, a marker of subclinical cardiac ischaemia, and subsequent renal function decline. Further research is required to establish the predictive value of hsTnT and response to intervention.

Risk of death following admission to a UK hospital with diabetic ketoacidosis.

AIMS/HYPOTHESIS: The aim of this study was to assess the risk of death during hospital admission for diabetic ketoacidosis (DKA) and, subsequently, following discharge. In addition, we aimed to characterise the risk factors for multiple presentations with DKA. METHODS: We conducted a retrospective cohort study of all DKA admissions between 2007 and 2012 at a university teaching hospital. All patients with type 1 diabetes who were admitted with DKA (628 admissions of 298 individuals) were identified by discharge coding. Clinical, biochemical and mortality data were obtained from electronic patient records and national databases. Follow-up continued until the end of 2014. RESULTS: Compared with patients with a single DKA admission, those with recurrent DKA (more than five episodes) were diagnosed with diabetes at an earlier age (median 14 [interquartile range 9-23] vs 24 [16-34] years, p < 0.001), had higher levels of social deprivation (p = 0.005) and higher HbA1c values (103 [89-108] vs 79 [66-96] mmol/mol; 11.6% [10.3-12.0%] vs 9.4% [8.2-10.9%], p < 0.001), and tended to be younger (25 [22-36] vs 31 [23-42] years, p = 0.079). Antidepressant use was greater in those with recurrent DKA compared with those with a single episode (47.5% vs 12.6%, p = 0.001). The inpatient DKA mortality rate was no greater than 0.16%. A single episode of DKA was associated with a 5.2% risk of death (4.1 [2.8-6.0] years of follow-up) compared with 23.4% in those with recurrent DKA admissions (2.4 [2.0-3.8] years of follow-up) (HR 6.18, p = 0.001). CONCLUSIONS/INTERPRETATION: Recurrent DKA is associated with substantial mortality, particularly among young, socially disadvantaged adults with very high HbA1c levels.

Metabolic parameters associated with arterial stiffness in older adults with Type 2 diabetes: the Edinburgh Type 2 diabetes study.

OBJECTIVE: Increased arterial stiffness, as measured by pulse wave velocity (PWV), is associated with increased cardiovascular risk in the general population. Few studies have examined factors associated with increased PWV in people with Type 2 diabetes. The aim of this study was to determine whether there was a link between PWV and clinical variables associated with central obesity, in men and women with Type 2 diabetes. RESEARCH DESIGNS AND METHODS: Eight hundred and sixty individuals [mean age (±SD) 69 (±4) years] from the Edinburgh Type 2 Diabetes Study, underwent applanation tonometry using a high-fidelity micromanometer. PWV was measured by sequentially recording electrocardiogram-gated carotid and femoral artery waveforms. RESULTS: Waist circumference (ß = 0.10, P < 0.01) and waist : hip ratio (ß = 0.10, P < 0.01) were independently associated with PWV, but not with BMI. In a stepwise multiple regression model, mean arterial pressure (ß = 0.26, P < 0.01) and age (ß = 0.23, P < 0.01) were strongly associated with PWV. The associations between the central obesity measures and PWV were independent of age, sex, duration of diabetes and metabolic factors associated with central obesity. Duration of diabetes (ß = 0.10, P < 0.01) and glycated hemoglobin (ß = 0.09, P < 0.01) were also found to be independent predictors of arterial stiffness. Obesity biomarkers such as C-reactive protein, leptin, tumour necrosis factor-α and interleukin-6 were not associated with arterial stiffness. CONCLUSION: Central obesity in people with Type 2 diabetes was associated with increased arterial stiffness. This association was independent of the conventional factors associated with central obesity and further studies are required to identify the mechanisms involved.

A patient with thyrotropinoma cosecreting growth hormone and follicle-stimulating hormone with low alpha-glycoprotein: a new subentity?

BACKGROUND: Thyrotropinomas are rare pituitary tumors. In 25 percent of cases there is autonomous secretion of a second pituitary hormone, adding to the clinical complexity. We report a patient with thyrotropin (TSH)-dependant hyperthyroidism along with growth hormone (GH) and follicle-stimulating hormone (FSH) hypersecretion but low alpha-glycoprotein (alpha-subunit) concentrations, a hitherto unique constellation of findings. SUMMARY: A 67-year-old Scottish lady presented with longstanding ankle edema, paroxysmal atrial fibrillation, uncontrolled hypertension, fine tremors, warm peripheries, and agitation. Initial findings were a small goiter, elevated serum TSH of 7.37 mU/L (normal range, 0.30-6.0 mU/L), a free-thyroxine concentration of 34.9 pmol/L (normal range, 9.0-24.0 pmol/L), a flat TSH response to TSH-releasing hormone, and serum alpha-subunit of 3.1 IU/L (normal, <3.0 IU/L). There was no evidence of an abnormal thyroid hormone beta receptor by genotyping. Serum FSH was 56.8 U/L, but the luteinizing hormone (LH) was 23.6 U/L (postmenopausal FSH and LH reference ranges both >30 U/L) Basal insulin-like growth factor I was elevated to 487 microg/L with the concomitant serum GH being 14.1 mU/L, and subsequent serum GH values 30 minutes after 75 g oral glucose being 19.1 mU/L and 150 minutes later being 13.7 mU/L. An magnetic resonance imaging pituitary revealed a macroadenoma. Pituitary adenomectomy was performed with the histology confirming a pituitary adenoma, and the immunohistochemistry staining showed positive reactivity for FSH with scattered cells staining for GH and TSH. Staining for other anterior pituitary hormones was negative. After pituitary surgery she became clinically and biochemically euthyroid, the serum IFG-1 became normal, but the pattern of serum FSH and LH did not change. CONCLUSION: This case of plurihormonal thyrotropinoma is unique in having hypersecretion of TSH, GH, and FSH with low alpha-subunit. Such a combination may represent a new subentity of TSHomas.

Clinical and radiological features of patients with macroprolactinaemia.

OBJECTIVES: Macroprolactin is a complex of prolactin (PRL) and IgG and may account for a significant proportion of cases of 'idiopathic hyperprolactinaemia'. In this study, we sought to determine the prevalence and clinical features of macroprolactinaemia in patients diagnosed with hyperprolactinaemia in our region, with a view to determining how patients with macroprolactinaemia should be investigated and managed. PATIENTS AND METHODS: An Immuno-1 automated immunoassay system with polyethylene glycol (PEG) precipitation was used to identify macroprolactin, with a recovery of 700 mU/l. The clinical records of 51 (44 female) were available for retrospective review. RESULTS: The mean (range) age of patients was 39.5 (18-82) years. The median (range) concentrations for the various forms of PRL were: total PRL 1130 mU/l (728-5116), monomeric PRL 240 mU/l (50-656) and macroprolactin 895 mU/l (381-4854). Classical symptoms of hyperprolactinaemia were present in 39% of patients, although in many there were other possible explanations for their symptomatology. Pituitary adenomas were identified in six out of 36 people who underwent neuroimaging. Five of these patients had a microadenoma and one had a 10-mm macroadenoma (although, in this patient macroprolactin was identified after the discovery of the tumour). There was no relationship between macroprolactin concentrations and the presence of hyperprolactinaemic symptoms or neuroimaging abnormalities. CONCLUSIONS: Macroprolactinaemia is a common occurrence in patients with hyperprolactinaemia, but associated symptomatology may not necessarily be linked. The neuroimaging abnormalities were also probably incidental findings and it is questionable whether neuroimaging is necessary when significant macroprolactinaemia is identified and the concentration of monomeric PRL is not elevated (using the Immuno-1 assay system, following PEG precipitation).