Associations between continuous glucose monitoring-derived metrics and HbA1c in patients with type 2 diabetes mellitus.

AIMS: The aim of this study was to define the relationship between time in range (TIR) and hemoglobin A1c (HbA1c) levels in patients with type 2 diabetes mellitus (T2DM). METHODS: The glycemic profile of 999 Japanese patients was analyzed with FreeStyle Libre Pro Continuous Glucose Monitoring (FLP-CGM) while they continued their prescribed glucose-lowering medications. FLP-CGM data recorded over 8 consecutive days were analyzed. RESULTS: The regression model for HbA1c on TIR was HbA1c = 9.4966-0.0309 × TIR. The predicted HbA1c level for TIR of 70% was 7.33% and is higher than reports subjecting mostly T1DM. The TIR corresponding to HbA1c 7.0% was 80.64%. The patients with low TIR tended to have long duration of diabetes, used high dose of daily insulin, high body mass index, high HbA1c, liver dysfunction and high triglyceride. Relatively higher percentages of patients of this group used sulfonylureas, glucagon like peptide-1 receptor agonists and insulin. CONCLUSIONS: Our data showed predicted HbA1c corresponding to TIR is largely depends on study population, thus is not uniform. Our results provide new insights on the management of T2DM. However, caution should be exercised in extending the HbA1C-TIR relationship using FLP-CGM to any other sensors since there could be a risk of hypoglycemia in doing so.

[Primary hyperparathyroidism complicated with flail chest due to severe osteoporosis].

We report a 61-year-old woman who was admitted to our hospital in August 2004 with severe hypercalcemia and osteoporosis. Although she was found to have hypercalcemia five years earlier, she has never been treated. The patient was transferred to our hospital for further management of a recently-identified left neck mass. Serum calcium level was 15.0 mg/dL and intact parathyroid hormone (PTH) 3,321 pg/mL. (99m)Tc-methoxyisobutylisonitrile (MIBI) scintigraphy showed marked accumulation in the left neck. We diagnosed the tumor as parathyroid gland tumor and it was enucleated surgically. Although serum Ca level returned to normal after surgery, the patient suffered multiple rib fractures, complicated with marked paradoxical breathing. Internal fixation of the thorax was necessary due to deterioration of the heart failure. Progression of severe osteoporosis was associated with multiple fractures of the ribs and other serious complications including congestive heart failure occurred after surgery, reflecting the extreme difficulty in treating this patient.

Successful treatment of insulinoma by a single daily dose of octreotide in two elderly female patients.

We report two cases of insulinoma in advanced age patients considered unsuitable for surgery, in whom single daily doses of octreotide successfully improved hypoglycemia and hyperinsulinemia. The biological half-life of octreotide is about 100 min, hence it is customary to use two or three administrations per day to prevent hypoglycemia in insulinoma patients. The first case was a 76-year-old woman who presented with hyperinsulinemic hypoglycemia. Computed tomography (CT) and magnetic resonance imaging did not identify a tumor in the pancreas but a 1.5-cm tumor was found in the pancreatic body on abdominal angiography and selective arterial calcium stimulation and hepatic venous sampling (ASVS) were compatible with insulinoma. The patient refused surgery, but was successfully treated with octreotide at 50 microg subcutaneous injection once daily. Since the treatment was started (1 year), she has not suffered hypoglycemia. Case 2 was an 85-year-old woman who presented with hyperinsulinemic hypoglycemia. CT identified a 1.5-cm tumor in the pancreatic uncus, but she was considered unsuitable for surgery due to advanced age, obesity and cardiopulmonary dysfunction. Octreotide at 100 microg subcutaneous injection once daily prevented further hypoglycemic attacks, but two months later, postprandial plasma glucose was elevated. Octreotide was gradually reduced to 50 microg once daily. Three years have passed since the treatment without any hypoglycemic attack. Successful treatment with octreotide once daily could be due to old-age-related slow metabolism and could be potentially considered as the treatment of choice for elderly patients with insulinoma especially those considered unsuitable for surgery.

Indication for nateglinide in type 2 diabetes mellitus.

Nateglinide is a novel rapid- and short-acting insulin secretagogue that ameliorates postprandial hyperglycemia by improving insulin secretory dynamics to a near normal level more effectively than sulfonylureas. Recent epidemiological studies have demonstrated that postprandial hyperglycemia can result in arteriosclerosis, and that advanced arteriosclerosis is present in the initial stage of impaired glucose tolerance. Since postprandial hyperglycemia could be well treated by nateglinide, we examined the background factors of type 2 diabetic patients to determine the optimal indication for nateglinide. Our results indicate that nateglinide is most effective in young and obese patients. Furthermore, fewer responders had microangiopathy or were previously on oral hypoglycemic agents or sulfonylureas compared with non-responders. Although nateglinide is generally indicated for patients with mild HbA1c level, the present findings indicate that the drug was effective in the aforementioned patients regardless of pretreatment HbA1c levels. In one obese patient, nateglinide improved late hyperinsulinemia to near normal secretory dynamics. Our findings suggest that nateglinide is a physiologically preferable and useful drug for early type 2 diabetes without microangiopathy.

A rare case of primary hyperparathyroidism with clear cell adenoma.

We report a 52-year-old woman who was noted to have elevated alkaline phosphatase (ALP), hypercalcemia (Ca: 11.7 mg/dL), and intact parathyroid hormone (intact PTH: 643.1 pg/mL), and then referred to our hospital with suspected hyperparathyroidism. Ultrasound examination of the neck and magnetic resonance imaging showed a mass region in the posterior aspect of the left lobe of the thyroid, and Tl-Tc subtraction scintigraphy showed Tl uptake at the same location. Based on laboratory and imaging studies, she was diagnosed with primary hyperparathyroidism. The excised parathyroid was a large mass measuring 6.8 x 2.8 x 1.9 cm in diameter and weighing 15.4 g. It was soft, covered with a thin capsule, did not infiltrate the thyroid parenchyma, and showed no evidence of malignant process. Histopathological examination showed that it was clear cell adenoma. There was no evidence of metastasis from the parathyroid tumor in other organs. The post-operative course was excellent, and serum PTH, Ca, and ALP levels returned to normal. Among parathyroid tumors, large adenomas are commonly considered to be more likely malignant, but in this case it was benign despite measuring more than 6 cm in diameter. The histopathological type of the adenoma was clear cell adenoma, a very rare type. We report a clear cell adenoma of the parathyroid gland, which has not been described previously in Japan.

[A case of Hypothyroid Graves' disease with extremely high titers of TSAb].

Graves' ophthalmopathy in hypothyroid state is called Hypothyroid Graves' Disease, which is a comparatively rare disease. We experienced a case of a 57 year old man with severe exophthalmos and diplopia, which are typical symptoms of Graves' opthalmopathy, and with an extremely high thyroid-stimulating antibody(TSAb) level. He also had a firm diffuse goiter and hypothyroidism with positive anti-thyroglobulin and anti-thyroid microsomal antigen. These findings suggested Hashimoto's thyroiditis. Severity of ophthalmopathy and TSAb level were improved during replacement therapy with T4. Although a thyroid stimulation-blocking antibody was also detected in this patient, we thought that hypothyroidism in this case was based on destructive change in the thyroid with Hashimoto's thyroiditis. Therefore, we should be aware of the fact that there are cases of hypothyroidism with Graves' ophthalmopathy and a high level of TSAb.

Virilizing adrenocortical adenoma with Cushing's syndrome, thyroid papillary carcinoma and hypergastrinemia in a middle-aged woman.

We report a rare case of virilizing adrenocortical adenoma complicated with Cushing's syndrome, thyroid papillary carcinoma and hypergastrinemia. A 45-year-old woman had a history of amenorrhea for 10 years, hypertension for 8 years, and diabetes mellitus for 3 years. Physical examination showed a masculinized woman with severe hirsutism, male-like baldness, deep voice, acne in the precordia, and clitorism. Plasma testosterone, DHEA-S and urinary 17-KS were high, and plasma cortisol level was it at the upper limit of the normal range, but it did not show a diurnal rhythm nor was suppressed by 2 and 8 mg of dexamethasone. Abdominal CT scan showed a left adrenal tumor (4.5 cm in size). Adrenal scintigram revealed uptake of the tracer on the left side, and plasma cortisol concentration was high in a blood sample from the left adrenal vein. Left adrenalectomy was performed. Histopathological features of resected adrenal tumor were consistent with those of adrenocortical adenoma, consisting of tumor cells with eosinophilic compact cytoplasm. Immunohistochemical staining for steroidogenic enzymes showed reactivity for P450sec, 3 beta-HSD, P450c17, P450c21 and P450c11. Plasma testosterone and cortisol levels decreased to the normal range postoperatively. The patient was also found to have a papillary thyroid carcinoma and hypergastrinemia. Our patient is a rare case of virilizing adrenocortical adenoma associated with Cushing's syndrome, thyroid papillary carcinoma, and hypergastrinemia.

[A case of hypothyroidism due to hashimoto disease that presented elevations of free T3 and free T4 by thyroid hormone autoantibodies].

When we commonly evaluate the thyroid function, we measure TSH, free T3 and free T4. However, there are some cases that are difficult to diagnose because of the existence of thyroid hormone autoantibodies. We experienced a case of a 14-year-old girl with diffuse struma whose TSH, free T3 and free T4 were elevated by detected with Amerlex M free T3 and free T4 kits, although she did not have any symptoms. As the free T4 level was low by the equilibrium dialysis method, we diagnosed this case as hypothyroidism due to chronic thyroiditis. Because we found thyroid hormone antibodies in her serum, we thought that this case presented pseudoelevations of free T3 and free T4 by the analogue method.