Errol Wilmshurst

Unrecognized Hypo- and Hyperglycemia in Well-Controlled Patients with Type 2 Diabetes Mellitus: The Results of Continuous Glucose Monitoring

The aim of this study was to determine the prevalence and extent of glycemic excursions (hypo- and hyperglycemic) in elderly patients with well-controlled type 2 diabetes using a Continuous Glucose Monitor System (CGMS) (Medtronic MiniMed). Elderly patients (>65 years old) with type 2 diabetes were recruited if their glycosylated hemoglobin (HbA1c) was <7.5% and if their oral hypoglycemic therapy included a sulfonylurea. Patients were asked to undergo two consecutive 72-h periods of continuous glucose monitoring at baseline and then again at 1 month (total 288 h). Patients were asked to record four self-monitored capillary blood glucose levels each day for calibration of the monitor and also to record meal times, exercise, and symptoms of hypoglycemia. The number of hyperglycemic (>144 mg/dL), hypoglycemic (<50 mg/dL), and borderline-hypoglycemic (50-65 mg/dL) events were determined (an event was defined as a glucose value that persisted for at least 15 min with or without symptoms). Twenty-five patients (21 men, four women) 73.9 +/- 4.4 years old with an HbA1c of 6.2 +/- 0.8% were each monitored for an average of 187.57 h. The mean glucose values were: fasting, 139 +/- 40 mg/dL; 2 h post-breakfast, 167 +/- 58 mg/dL; 2 h post-lunch, 157 +/- 53 mg/dL; and 2 h post-dinner, 149 +/- 49 mg/dL. Twenty patients (80%) experienced a total of 103 hypoglycemic events, and 14 of these patients experienced 54 events where the glucose levels were </=40 mg/dL. Twenty-four patients (96%) experienced borderline-hypoglycemia (n = 229 events). Patients experienced a mean of 0.62 +/- 0.72 episodes of hypoglycemia (interstitial glucose <50 mg/dL) per day (four to five episodes overall), 0.35 +/- 0.6 episodes per day where the interstitial glucose was </=40 mg/dL (two to three episodes overall), and 1.37 +/- 1.22 episodes of borderline-hypoglycemia (nine to 10 episodes overall). Each episode of hypoglycemia persisted for 78 +/- 73 min, and borderline-hypoglycemia for 45 +/- 11 min. Patients were hypoglycemic 3.3% of the time and borderline-hypoglycemic 3.7% of the time. No episode of hypoglycemia was recorded by any patient in his or her daily diary. High postprandial glucose values (>144 mg/dL 2 h postprandial) were recorded after 57% of all meals (breakfast 60%, lunch 57.5%, dinner 55.2%). The CGMS was generally well tolerated, but 52% of patients could not be studied for the full 12 days of monitoring. Thus hypoglycemia and excessive postprandial glycemic excursions are common in well-controlled patients with type 2 diabetes treated with a sulfonylurea with or without metformin. The CGMS is a useful research and clinical tool to assess glycemia in patients with type 2 diabetes but is not tolerated by all subjects.

Outcome of pregnancies complicated by pre‐gestational diabetes mellitus

Pregestational diabetes mellitus (DM) is associated with adverse fetal and maternal outcomes. Studies suggest that optimal control of diabetes before and during pregnancy minimises these risks. There are few recent reviews of outcomes of pregnancies complicated by DM in Australia.

Cardiac function in acute hypothyroidism

It has been established that chronic hypothyroidism may affect cardiac function by several mechanisms. It is not known how long the patient has to be hypothyroid for cardiac involvement to develop. This study was undertaken to assess the effect of a short period of hypothyroidism (10 days) on cardiac function. Nine patients who had had total thyroidectomy, had received ablative radioiodine for thyroid cancer and were euthyroid on replacement therapy were studied while both euthyroid and hypothyroid. Cardiac assessment was performed by X-ray, ECG, echocardiography and gated blood-pool scans. After 10 days of hypothyroidism, the left-ventricular ejection fraction failed to rise after exercise in 4 of the 9 patients studied, which was significant (P0.002). No significant changes in cardiac size or function at rest were detected. This functional abnormality in the absence of any demonstrable change in cardiac size and the absence of pericardial effussion with normal basal function suggest that short periods of hypothyroidism may reduce cardiac reserve, mostly because of alterations in metabolic function.

The Relationship of Prorenin Values to Microvascular Complications in Patients with Insulin-Dependent Diabetes Mellitus

We have performed a cross-sectional analysis of the relationship between prorenin values and the microvascular complications of diabetes in a well controlled population of insulin-dependent diabetes mellitus (IDDM) subjects. One hundred and thirty-nine subjects (75 men, 64 women, age 44 +/- 17 years; duration of diabetes 19 +/- 15 years), formed the study group. Sixty-seven subjects (48.2%) had no complications, 55 (39.6%) had retinopathy alone, and 17 (12.2%) had retinopathy and albuminuria. Patients with no complications had lower prorenin values than those with microvascular complications (p < 0.001), whilst patients with both albuminuria and retinopathy had higher values than those with retinopathy alone (p < 0.05). Retinopathy was associated with duration of diabetes (p < 0.0001), diastolic blood pressure (p < 0.02) and albuminuria (p < 0.0001) while albuminuria was associated with prorenin (p < 0.02), serum triglyceride (p < 0.01) and retinopathy (p < 0.001). Patients with albuminuria were 5.5 times more likely to have raised prorenin values (>80 ng/mL/h) than those with normal albumin excretion [95% confidence interval (CI): 1.48-20.12] and those with retinopathy alone were 2.5 times as likely (95% CI: 1.19-5.15). Eighty patients with IDDM (40 males, 40 females; age: 47 +/- 17 years; duration of diabetes: 20 +/- 15 years), had retinal photography performed to determine the association between the severity of retinopathy and prorenin values. Retinopathy was more severe in patients with retinopathy and albuminuria than in those with retinopathy alone (p < 0.002). When the prorenin values of patients with more marked retinopathy (eye grade greater than 3) were compared, prorenin values of those with retinopathy and albuminuria were greater than those of patients with retinopathy alone [269 (139-1406) versus 91 (41-273) ng/mL/h: geometric mean (range); p < 0.05]. Furthermore, when patients without albuminuria were considered, there was no significant difference between the prorenin levels of patients with more severe retinopathy (eye grade >3) when compared to patients with lesser degrees of retinopathy [91 (41-273) versus 69 (23-375). In patients with microvascular complications, prorenin values were independently predicted by albuminuria (p < 0.0001) and diastolic blood pressure (p < 0.02) but not the severity of retinopathy. In conclusion, prorenin values are significantly associated with the presence of microvascular complications in patients with IDDM. The association with albuminuria may be stronger than the association with retinopathy.

Intravenous pamidronate in the treatment and prevention of osteoporosis

Abstract

Measuring renal function in patients with diabetes mellitus

We estimated the glomerular filtration rate in 33 patients from our diabetic clinic using three methods: the creatinine clearance measured from a timed urine sample and a serum creatinine; the creatinine clearance calculated from the serum creatinine according to the formula of Cockcroft and Gault; and, the plasma clearance of ethylenediaminetetra-acetic acid (EDTA) labeled with 51Cr ([51Cr]EDTA). We repeated the measurements in seven subjects. The measured creatinine clearance was not reproducible. The other two methods were correlated, but not according to the formula y = x. The calculated creatinine clearance significantly underestimated the [51Cr]EDTA clearance particularly at higher [51Cr]EDTA clearance rates. [51Cr]EDTA clearance has been shown by others to parallel, but underestimate, inulin clearance, the optimal method of estimating glomerular filtration rate but difficult to perform in routine practice. Accurately measuring renal function in routine clinical practice is difficult, and this must be borne in mind when making clinical decisions based on current measurements.

Mortality associated with primary hyperparathyroidism.

561 patients with primary hyperparathyroidism were followed between 1961 and 1994. Relative survival was compared to that of the Australian population studied during the same time interval. Mortality was significantly greater in the hyperparathyroid population (P<0.001). Mortality was not greater in the patients with serum calcium levels >3.00 mmol/L compared to those with a serum calcium levels <3.00 mmol/L. 113 patients did not have parathyroid surgery. Their relative survival was not significantly different from those who had surgery but their mean serum calcium and parathyroid hormone (PTH) levels were significantly lower than those who had surgery. A re-analysis of the 453 patients followed between 1972 and 2011 was carried out and a 20-year survival analysis made of those diagnosed between 1972 and 1981 and those diagnosed between 1982 and 1991. The latter group had significantly worse relative mortality than the former group (P<0.001) but was significantly older at the time of diagnosis (56.94 ± 14.83 vs 52.01 ± 13.58, P<0.001). The serum calcium and serum PTH levels were not significantly different between these two groups.

The measurement of antithyroglobulin autoantibodies in the presence of thyroglobulin

An homogeneous phase radioassay (HRA) for antithyroglobulin autoantibodies (TgAb) in serum was investigated. In this method TgAb is allowed to react with 125l-Tg in solution and the immune complexes formed are separated by precipitation with sheep anti-human gammaglobulin. HRA proved to be suitable for the screening of sera prior to thyroglobulin (Tg) radioimmunoassay; being both sensitive, and unaffected by high endogenous levels of Tg. HRA was more sensitive than either of two commercial TgAb kits; a hemagglutination assay (Wellcome Australia Ltd.) and a solid phase radioassay (CIS France). Positive responses were obtained with 4 out of 42 normal subjects (titers up to 1/10), 24 out of 31 with untreated Graves’ disease (titers up to 1/10,000) and all out of 18 with Hashimoto’s thyroiditis (titers up to 1/10,000). Binding of 125l-Tg was displaceable with added unlabelled Tg, but in no case could it be abolished with less than 1,000 μg/l. Some sera exhibited more than one class of binding site and variation in both affinity and capacity for Tg was observed. It was concluded that the use of an assay standard for the reporting of results in units of concentration is invalid, although units of TgAb activity may be used as long as the analytical method is specified. Serum levels of TgAb may also be reported in semi-quantitative terms, such as in this report where a binding titer is used, or alternatively, antigen binding capacity may be reported.