Metabolic management restores thyroid function in adults with type 2 diabetes
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Adults in China with type 2 diabetes had improved glucose control and a restoration of thyroid function after participating in metabolic management, according to a study published in the Journal of Diabetes.
“Patients with type 2 diabetes had significantly lower levels of free triiodothyronine
and free thyroxine within normal reference range than patients with normal glucose tolerance and prediabetes,” Yufan Wang, MD, PhD, professor in the department of endocrinology and metabolism at Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, and colleagues wrote. “Free T3 and ree T4 levels were negatively associated with HbA1c level and positively associated with estimated glucose disposal rate. After National Metabolic Management Center standardized management, the metabolic status in the diabetes uncontrolled group dramatically improved ... Thyroid hormone levels were restored to normal after metabolic status improved in type 2 diabetes patients.”
Researchers recruited 2,000 participants who were undergoing treatment at the National Metabolic Management Center of Shanghai General Hospital and had a community physical examination from September 2017 to August 2019. Participants were split into four groups based on blood glucose level at baseline: individuals without diabetes (n = 132), with prediabetes (n = 147), well-controlled diabetes for individuals with type 2 diabetes and an HbA1c of 7% or less (n = 505) and uncontrolled diabetes for with type 2 diabetes and an HbA1c of more than 7% (n = 1,216). Participants in the diabetes groups received standardized management care at the National Metabolic Management Center, where they could receive services including examinations, evaluation, prescriptions and health education.
At baseline, the group had the highest mean levels of free T3 (4.76 pmol/L) and free T4 (17.74 pmol/L), followed by the prediabetes group (mean free T3 4.72 pmol/L; mean free T4 16.74 pmol/L). The controlled diabetes cohort had a lower mean free T3 of 4.59 pmol/L and a lower mean free T4 of 15.65 pmol/L than the group without diabetes and the prediabetes cohort. The uncontrolled diabetes group also had lower mean free T3 (4.46 pmol/L) and free T4 levels (15.69 pmol/L). There was no significant difference in thyroid-stimulating hormone between the four groups.
After adjusting for age, sex, use of drugs, use of lipid-lowering drugs, diabetes duration, BMI and waist-hip ratio, free T3 was negatively correlated with fasting plasma glucose and positively correlated with estimate glucose disposal rate in the two diabetes groups. No relationship was found between and blood glucose levels.
Researchers followed up with 254 individuals in the uncontrolled diabetes group 1 year after baseline (mean age, 49.4 years). The cohort showed improvement in most metabolic parameters at 1 year, with mean FPG decreasing from 7.8 mmol/L at baseline to 6.5 mmol/L at follow-up, postprandial plasma glucose decreasing from 14.3 mmol/L at baseline to 10.9 mmol/L at follow-up, and mean HbA1c dropping from 8.7% at baseline to 6.7% at follow-up. The mean estimated glucose disposal rate increased from 7.59 mg/kg/min to 8.86 mg/kg/min (P < .001 for all).
Concentrations of free T3 increased in the follow-up group from 4.51 pmol/L at baseline to 4.68 pmol/L after year (P < .05). No significant difference was found in T4 levels. Reverse T3 decreased from 1.03 nmol/L at baseline to 0.92 nmol/L at follow-up and dropped from 2.18 mIU/L to .7 mIU/L (P < .001).
Researchers also followed up with 82 adults in the well-controlled diabetes cohort. The group had improved , BMI and waist-hip ratios at follow-up, whe HbA1c remained unchanged. decreased from 2.42 mIU/L at baseline to mIU/L at follow-up (P < .05) and reverse T3 levels decreased from 1.04 nmol/L to 0.94 nmol/L.
“Our study suggested that low free thyroid hormone levels in normal range were significantly associated with high glucose level and severe insulin resistance,” researchers wrote. “For poorly controlled type 2 diabetes, Metabolic Management Center -year standardized management not only improved blood glucose levels, insulin resistance and other metabolic indicators, but restored thyroid function as well.”
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At baseline, after adjustment for multiple covariates, including BMI, serum free T3 and free T4 levels were higher in normoglycemic and prediabetes patients than in those with diabetes, and higher in patients with hemoglobin A1c >7% than in diabetes patients with good glycemic control. Serum free T3 levels were inversely correlated with Hgb A1c and fasting blood glucose levels, while there was no association with serum TSH.
It is not specified exactly what interventions were carried out in the patients with diabetes, but following one year of management which included “evaluation, prescriptions, and health education," BMI, blood pressure, serum lipids, and hemoglobin A1c were all reduced in the 254 patients who had uncontrolled type 2 diabetes at baseline. Serum free T3 had increased, and both serum TSH and reverse T3 levels had decreased.
Hypothyroidism is more common among patients with type 2 diabetes than it is in the general population, and thyroid hormone is known to influence glucose metabolism in multiple ways, including by regulation of glucose homeostasis via effects on liver, adipose tissue, the central nervous system, skeletal muscle, and pancreatic beta cells.
The use of a multi-pronged metabolic intervention makes it challenging to understand how much of the observed shift in thyroid hormone levels over the course of this study may have been mediated directly by improved glycemic control, how much by weight change (typically TSH and FT3 are both increased and FT4 is decreased in obese individuals; levels normalize with weight loss), and how much by medications (metformin is known to lower serum TSH). The observed decrease in reverse T3 levels after the metabolic intervention suggests a decrease in type 3 deoiodinase activity, perhaps mediated by decreased oxidative stress. Larger prospective studies will be needed to better tease out these relationships and to understand both whether diabetes treatment causes clinically meaningful improvements in thyroid function and whether improved thyroid status might lower diabetes risk.
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