c-peptide and Graves-Disease

Hyperthyroidism is considered to be an insulin-resistant state, but a quantitative evaluation of some action of insulin is still lacking. We performed euglycaemic clamp at about 350 and 7000 pmol l-1 plasma insulin concentration in combination with the 3H-glucose infusion in 12 patients with Graves' disease and in 12 matched controls. Fasting plasma insulin (126 +/- 6.5 vs. 77.5 +/- 5.7 pmol l-1; P less than 0.001), C-peptide (502 +/- 36 vs. 363 +/- 41 pmol l-1; P less than 0.001) and glucagon (47 +/- 3.3 vs. 33.3 +/- 3 pmol l-1; P less than 0.01) were significantly higher in hyperthyroids than in euthyroids. Basal hepatic glucose production was significantly higher in hyperthyroids than in euthyroids (18.3 +/- 1.4 vs. 9.2 +/- 0.5 mumol l-1; P less than 0.0001), and its suppression during physiological hyperinsulinaemia was only 50% in hyperthyroids. Glucose utilization and suppression of lipolysis were normally stimulated by insulin. All parameters altered during hyperthyroidism were normalized during methimazole-induced euthyroidism. We conclude that insulin resistance involves mainly glucose rather than lipid and is selective at the hepatic level.

Topics: Adult; Blood Glucose; C-Peptide; Female; Glucagon; Glucose; Graves Disease; Humans; Insulin; Insulin Resistance; Insulin Secretion; Liver; Male; Middle Aged

Autoimmune diseases, including autoimmune endocrine diseases (AIED), are thought to develop following environmental exposure in patients with genetic predisposition. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and vaccines against it could represent new environmental triggers for AIED. We report a patient, with history of vitiligo vulgaris and 8 years of type 2 diabetes, who came to our institution because of fever, weight loss, asthenia and thyrotoxicosis occurred 4 weeks later the administration of BNT162B2 (Pfizer-BioNTech) SARS-CoV-2 vaccine. Clinical, biochemical and instrumental work-up demonstrated Graves' disease and autoimmune diabetes mellitus. The occurrence of these disorders could be explained through different mechanism such as autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome), mRNA "self-adjuvant" effect, molecular mimicry between human and viral proteins and immune disruption from external stimuli. However further studies are needed to better understand the underlying pathogenesis of AIED following SARS-CoV-2 vaccine.

Topics: Adjuvants, Immunologic; Autoantibodies; BNT162 Vaccine; C-Peptide; COVID-19; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Glycemic Control; Graves Disease; Humans; Male; Middle Aged; Molecular Mimicry; SARS-CoV-2; Thyrotoxicosis; Vitiligo

To observe the glycemic variation (GV) in uncontrolled Graves' disease (GD) patients with normal glucose metabolism measured by continuous glucose monitoring (CGM).. This was a single-center, open-label, observational study. From January 2017 to October 2017, 20 GD patients with normal glucose metabolism and 24 healthy control subjects were recruited. Serum samples were obtained at 0, 30, and 120 min after oral glucose loading for glucose, insulin, and C-peptide level measurements. Fasting plasma fasting free triiodothyronine (FT3), free thyroxin (FT4), and thyroid stimulating hormone concentrations were also detected. All participants were subjected to a 3-day CGM after baseline data were collected. The primary endpoint was the difference in the mean amplitude of the glycemic excursions between the two groups.. Compared with the healthy subjects, the GD patients had higher mean amplitude of glycemic excursions (MAGE) (P < 0.01). Multiple linear stepwise regression analysis showed that FT4 level was an independent factor for the MAGE. Interestingly, the GD patients had a significant prolongation in the time to peak glucose, especially after breakfast (P < 0.01), and the elevation in the incremental area under the curve of glucose after breakfast till 4 hours later.. Uncontrolled GD patients with normal glucose metabolism had a greater GV, and the FT4 level may contributed to the increased GV.

Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; C-Peptide; Female; Glycated Hemoglobin; Graves Disease; Humans; Insulin; Male; Middle Aged; Thyroid Hormones

Topics: Adult; Amylases; Autoantibodies; Biomarkers; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Female; Glucagon; Graves Disease; Humans; Ketone Bodies; Lipase; Pregnancy; Pregnancy in Diabetics

To study the clinical significance of thyroid autoantibodies in Thai patients with type 1 diabetes and their relationship with glutamic acid decarboxylase antibodies (GAD(65)Ab).. Thyroglobulin antibodies (TG-Ab) and thyroid peroxidase antibodies (TPO-Ab) were measured in 50 Thai type 1 diabetic patients. Forty-four patients also had GAD(65)Ab measured. Serum thyrotropin (TSH) was measured in all patients who had no history of thyroid disease regardless of thyroid antibody status. Clinical data including sex, age at onset and duration of diabetes, family history of diabetes, fasting c-peptide levels as well as frequencies of GAD(65)Ab were compared between patients with and without thyroid antibodies. GAD(65)Ab was also measured in 29 non-diabetic patients with hyperthyroid Graves' disease or Hashimoto thyroiditis as a control group.. TG-Ab and TPO-Ab were positive in nine (18%) and 15 (30%) patients, respectively. Eight patients (16%) were positive for both antibodies. Two of 16 patients who were positive for TG-Ab or TPO-Ab had a previous history of hyperthyroidism prior to diabetes onset. Of the remainder, two were newly diagnosed with hyperthyroidism and one was found to have clinical hypothyroidism at the time of the study. None of 34 patients without thyroid antibodies had thyroid dysfunction. Eight patients with positive thyroid antibodies but without clinical thyroid dysfunction and 21 patients without thyroid antibodies were followed for up to 3 years, two patients of the first group developed hypothyroidism, whereas none of the latter developed thyroid dysfunction. The frequency of thyroid dysfunction at the time of initial study was significantly higher in patients with positive thyroid antibodies (3/14 vs. 0/34; P=0.021) and these patients who were initially euthyroid tended to have a higher risk of developing thyroid dysfunction (2/8 vs. 0/21; P=0.069). The frequency of thyroid antibodies was significantly increased in females and in those who had positive GAD(65)Ab. GAD(65)Ab was negative in all of the non-diabetic patients with autoimmune thyroid disease.. About one-fourth of Thai patients with type 1 diabetes without thyroid disease had thyroid antibodies. The frequency of thyroid antibodies was increased in female and in GAD(65)Ab positive patients. The presence of thyroid antibodies is associated with a higher frequency of and may predict a higher risk for thyroid dysfunction in Thai type 1 diabetic patients.

Topics: Adult; Age of Onset; Asian People; Autoantibodies; C-Peptide; Diabetes Mellitus, Type 1; Female; Glutamate Decarboxylase; Graves Disease; Humans; Iodide Peroxidase; Isoenzymes; Male; Thailand; Thyroglobulin; Thyrotropin

Autoantibodies to the 64,000-M(r) (64K) islet cell protein, identified as glutamic acid decarboxylase, were assayed in 46 Type 1 (insulin-dependent) diabetic patients with a disease duration of more than 5 years. Of 46 Type 1 diabetic patients, 18 (39.1%) were found to be positive for 64K antibodies and 12 of these patients had been diagnosed with autoimmune thyroid disease. Serum C-peptide levels were not detectable in 15 of 18 patients positive for 64K antibodies. The samples were also tested for titres of islet cell antibodies. Islet cell antibodies were detected in 15 (32.6%) of the 46 patients and all the islet cell antibody positive patients were also found to be positive for 64K antibodies. Furthermore, of these 15 patients 12 had previously been diagnosed with autoimmune thyroid disease. A correlation between levels of 64K antibodies and islet cell antibody titre revealed that higher levels of 64K antibodies were observed in patients who had higher islet cell antibody titre. These results demonstrate that most long-term Type 1 diabetic patients with 64K antibodies were also positive for islet cell antibodies complicated by autoimmune thyroid disease.

Topics: Adult; Autoantibodies; C-Peptide; Diabetes Mellitus, Type 1; Female; Glutamate Decarboxylase; Graves Disease; Humans; Islets of Langerhans; Male; Molecular Weight; Thyroid Function Tests; Thyroiditis, Autoimmune

To examine the effect of hyperthyroidism on carbohydrate metabolism, we studied glucose-stimulated insulin secretion and glucose utilization in 8 subjects with Graves' disease before and after treatment for hyperthyroidism and 8 age-, sex- and weight-matched normal subjects. Subjects with Graves' disease had significant elevated serum levels of thyroxine (24.81 +/- 2.44 micrograms/dl, mean +/- SEM) and triiodothyronine (459 +/- 5.5 ng/dl, mean +/- SEM). Simultaneous measurement of plasma glucose, serum insulin and C-peptide levels during fasting and every 30 minutes up to 180 minutes after 75 g oral glucose loading was determined. In addition, plasma glucose, serum insulin and serum C-peptide were measured during euglycemic glucose clamp with insulin infusion of 40 mU/m2 min-1. Mean fasting plasma glucose (P less than 0.05, serum insulin (P less than 0.005) and serum C-peptide (P less than 0.005) levels were significantly higher in the hyperthyroid patients. After glucose loading, the plasma glucose (P less than 0.05), serum insulin (P less than 0.05) and C-peptide (P less than 0.05) responses were significantly higher in hyperthyroid patients at all times up to 180 minutes. During euglycemic clamp studies, the steady-state serum insulin levels were identical in the two groups. The glucose disposal rate was lower in hyperthyroid patients before treatment (P less than 0.01) than in normal subjects. After thyroid function had been normalized for 2 to 4 weeks, the glucose disposal rate increased significantly (P less than 0.05), but was still significantly lower than those of normal subjects (P less than 0.05). Our data show that patients with Graves' hyperthyroidism manifest glucose intolerance, hyperinsulinemia and insulin resistance.

Topics: Administration, Oral; C-Peptide; Female; Glucose; Graves Disease; Humans; Hyperthyroidism; Insulin; Insulin Secretion; Male; Thyroxine; Triiodothyronine

Insulin resistance in hyperthyroidism seems to depend on increased glucose production rather than on decreased glucose utilization. A decreased insulin binding on different target cells has been reported in patients in whom an in vivo evaluation of peripheral insulin sensitivity was lacking. In 20 patients with Graves' disease (6 males, 14 females), aged 40.0 +/- 2.0 yr, BMI 23.7 +/- 0.7, and in 20 well-matched controls we performed the following tests: 75 g o.G.T.T., euglycemic-hyperinsulinemic clamp at 50 microU/ml combined with D-[3-3H] glucose infusion in tracer amounts, in vitro insulin binding on circulating monocytes. Fasting plasma glucose values were similar in the two groups, whereas plasma insulin values were significantly higher in hyperthyroids (21.4 +/- 2.5 vs 10.6 +/- 0.6 microU/ml, p less than 0.01). The values of peripheral glucose utilization (5.61 +/- 0.24 vs 6.01 +/- 0.22 mg/kg-min) and of total specific insulin binding (4.07 +/- 0.20 vs 4.39 +/- 0.23% bound to 10(7) cells/ml) were not significantly different in the two groups. These results indicate that in vitro and in vivo data, when recorded in the same patients, are concordant to confirm a normal peripheral tissue sensitivity to insulin in Graves' disease.

Topics: Adult; Blood Glucose; C-Peptide; Female; Glucose Tolerance Test; Graves Disease; Humans; Insulin; Male; Metabolic Clearance Rate; Monocytes; Thyroid Hormones

Topics: Adolescent; Autoantibodies; C-Peptide; Female; Glucose Tolerance Test; Graves Disease; Humans; Insulin Antibodies; Methimazole; Syndrome

Sensitivity to porcine insulin has been compared in overnight fasted hyperthyroid and control subjects using a euglycaemic clamp technique. Basal values for blood glucose, lactate, pyruvate, alanine, serum insulin and C-peptide were similar in the two groups, whilst blood glycerol (hyperthyroid 0.11 +/- 0.02 (mean +/- S.E.) vs. control 0.06 +/- 0.01 mmol/l, P less than 0.01) and blood 3-hydroxybutyrate (0.28 [0.03-0.79, range ]vs 0.09 [0.01-0.29 ]mmol/l, P less than 0.05) were increased in hyperthyroidism. During the 2 hour insulin infusion (0.05 U/kg/h), serum insulin plateaued at the same level (44 +/- 4 vs 44 +/- 1 mU/l) and insulin metabolic clearance rates were similar (1.21 +/- 0.10 vs 1.25 +/- 0.03 l/min). Serum C-peptide levels also decreased by similar amounts (40 +/- 8 vs 47 +/- 6%). The amount of glucose infused to maintain euglycaemia was identical during the second hour of insulin infusion (290 +/- 50 vs 330 +/- 30 mg/kg) as were the increments in lactate and pyruvate concentrations. Blood glycerol values decreased in both groups although values in hyperthyroid patients remained significantly higher than in controls. 3-Hydroxybutyrate concentrations fell to similar values in the two groups. These findings suggest that insulin-stimulated glucose metabolism and inhibition of ketogenesis are normal in hyperthyroidism.

Topics: 3-Hydroxybutyric Acid; Adult; Blood Glucose; C-Peptide; Female; Glucose; Glycerol; Graves Disease; Humans; Hydroxybutyrates; Infusions, Parenteral; Insulin; Lactates