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Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders
Open accessAbstract
Thyroid dysfunction and diabetes mellitus are closely linked. Several studies have documented the increased prevalence of thyroid disorders in patients with diabetes mellitus and vice versa. This review critically discusses the different underlying mechanisms linking type 1 and 2 diabetes and thyroid dysfunction to demonstrate that the association of these two common disorders is unlikely a simple coincidence. We assess the current state of knowledge on the central and peripheral control of thyroid hormone on food intake and glucose and lipid metabolism in target tissues (such as liver, white and brown adipose tissue, pancreatic β cells, and skeletal muscle) to explain the mechanism linking overt and subclinical hypothyroidism to type 2 diabetes and metabolic syndrome. We also elucidate the common susceptibility genes and the pathogenetic mechanisms contributing to the autoimmune mechanism involved in the onset of type 1 diabetes mellitus and autoimmune thyroid disorders. An untreated thyroid dysfunction can impair the metabolic control of diabetic patients, and this association can have important repercussions on the outcome of both of these disorders. Therefore, we offer recommendations for the diagnosis, management, and screening of thyroid disorders in patients with diabetes mellitus, including the treatment of diabetic patients planning a pregnancy. We also discuss the major causes of failure to achieve an optimal management of thyroid dysfunction in diabetic patients and provide recommendations for assessing and treating these disorders during therapy with antidiabetic drugs. An algorithm for a correct approach of these disorders when linked is also provided.
Overview
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Written from the paper’s full text.
TL;DR
This review argues that thyroid dysfunction (TD) and diabetes mellitus (DM) are closely associated through shared autoimmunity, thyroid hormone effects on glucose/lipid metabolism, and drug interactions. It summarizes prevalence, mechanisms, prognosis, and management/screening recommendations, emphasizing that untreated TD can impair metabolic control in patients with diabetes.
Key findings
- Autoimmune thyroid disease occurs in 17% to 30% of adults with type 1 diabetes (T1D), and autoimmune hypothyroidism is present in 25% of children with T1D.
- TD is more common in type 2 diabetes (T2D) than in the general population; hypothyroidism prevalence in T2D ranges from 6% to 20%, and a meta-analysis found a 1.93-fold higher pooled prevalence of subclinical hypothyroidism in T2D versus healthy controls (95% CI, 1.66 to 2.24).
- Subclinical hypothyroidism in T2D was associated with increased risks of diabetic nephropathy (OR 1.74; 95% CI, 1.34 to 2.28), diabetic retinopathy (OR 1.42; 95% CI, 1.21 to 1.67), peripheral arterial disease (OR 1.85; 95% CI, 1.35 to 2.54), and diabetic peripheral neuropathy (OR 1.87; 95% CI, 1.06 to 3.28), but not coronary heart disease.
- Hyperthyroidism is found in 4.4% of adults with T2D, and subclinical hyperthyroidism in ~2% to 4%; preexisting DM is exacerbated by hyperthyroidism, and insulin treatment should be adjusted after TD occurs. Metformin lowers TSH in overt and subclinical hypothyroidism but not in euthyroid patients, with a TSH cut-off of 2.5 to 3 mU/L predicting the effect.
Methods
- Narrative review based on personal files, MEDLINE articles, meta-analyses, references of relevant articles and textbooks published from 1977 to 2018, and recent international guidelines.
- Search terms included thyroxine, triiodothyronine, hypothyroidism, hyperthyroidism, subclinical thyroid disease, type 1 and type 2 diabetes mellitus, insulin resistance, metabolic syndrome, gestational diabetes, prevalence, incidence, deiodinases, glucose metabolism, lipid metabolism, adipose tissue, appetite regulation, skeletal muscle, screening, morbidity, and mortality.
- The authors performed a critical assessment of the literature, agreed on inclusion/exclusion criteria, preferred high-quality papers, meta-analyses, randomized controlled and longitudinal trials, and discussed limitations in study design or execution when identified.
Limitations
- The paper states that limitations in study design or execution were discussed when identified, but it is a narrative review without new primary data and relies heavily on observational studies, meta-analyses, and guideline documents.
- The authors note insufficient evidence to determine specific screening tests, exact screening intervals, and cost-benefit for TD screening in T2D; they also note no prospective randomized controlled trial evaluating whether treating subclinical hyperthyroidism improves adverse outcomes.
- The text reports heterogeneity among included studies in meta-analyses of subclinical hypothyroidism and metabolic syndrome, conflicting results from Danish register-based studies on TD and diabetes incidence, and inconsistent findings on the D2 Thr92Ala polymorphism and insulin resistance/T2D.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Asymptomatic TD is frequently observed in patients with T2D.”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Screening of TD in patients with T2D
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The diagnosis of TD in patients with T2D is difficult because some oral antidiabetic drugs can interfere with the evaluation of serum TSH levels.”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Screening of TD in patients with T2D
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Both hyperthyroidism and hypothyroidism can impair the metabolic control in patients with diabetes.”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Abstract
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In the paper
“Thyroid dysfunction and diabetes mellitus are closely linked.”
- Also stated in: § Abstract · plain
“DM and thyroid disease are two closely associated disorders.”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Abstract
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“to demonstrate that the association of these two common disorders is unlikely a simple coincidence.”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Abstract
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In the paper
“TD is associated with changes in body weight and composition, body temperature, and total and resting energy expenditure independently of physical activity (, , ).”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Obesity
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In the paper
“Oppositely, the correction of hyperthyroidism may be responsible for excessive weight gain, independent of the treatment modality of thyrotoxicosis, that is, surgery, RAI, or ATDs ().”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Effects of hypothalamic pituitary thyroid axis on appetite regulation
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In the paper
“In healthy euthyroid middle-aged subjects, FT and FT levels and the FT/ FT ratio were associated with various markers of unfavorable metabolic profile and cardiovascular risk ().”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Insulin resistance
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In the paper
“Alternatively, individuals who are morbidly obese show a high prevalence of overt and subclinical autoimmune hypothyroidism, accounting for .% of hypothyroidsm (, ).”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Obesity
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In the paper
“The TH plays a major role in regulating both obligatory and adaptive thermogenesis by increasing the basal metabolic rate and by modulating the sympathetic nervous system activation of BAT (, ) (Fig. ).”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Effects of TH on thermogenesis
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- It may state two separate claims as one. 46
- Probably not a substantial claim. 6
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“An untreated thyroid dysfunction can impair the metabolic control of diabetic patients, and this association can have important repercussions on the outcome of both of these disorders.”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Abstract
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In the paper
“Several studies have documented the increased prevalence of thyroid disorders in patients with diabetes mellitus and vice versa.”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Abstract
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In the paper
“The expression of UCP is required for BAT thermogenesis, and UCP is synergistically regulated by both noradreanaline and T ().”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Effects of TH on thermogenesis
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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In the paper
“Regarding the effects of insulin on the thyroid gland, high circulating levels of insulin may induce increased thyroid proliferation with the development of larger thyroid volume and the formation of nodules.This goitrogenic action of insulin may explain why the thyroid gland was considered another victim of the insulin resistance syndrome ().”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Insulin resistance
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In the paper
“Both AITD and female sex are risk factors for progression of TD among patients with diabetes.”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Risk of progression of TH deficiency in T2D
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In the paper
“Regarding hypothyroidism, weight excess was reported in % patients with overt hypothyroidism, reflecting both the accumulation of body fat, due to decreased resting energy expenditure, and the increased water content of the body, consequent to a reduced capacity of excreting free water ().”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Effects of hypothalamic pituitary thyroid axis on appetite regulation
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is interesting that this IRS/ phosphatidylinositol--OH kinase pathway is also activated by leptin, and therefore the similar effects of leptin and insulin on food intake may be mediated via this common pathway in the hypothalamus ().”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Effects of hypothalamic pituitary thyroid axis on appetite regulation
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“The central infusion of BDNF reduces food intake and induces weight loss in rats ().”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Effects of hypothalamic pituitary thyroid axis on appetite regulation
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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In the paper
“Overt hypothyroidism is associated with hyperlipidemia, and even SHypo has been related to alterations in plasma lipids, although with conflicting results ().”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Lipids, blood pressure, and nonalcoholic fatty liver disease
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“This disorder is closely associated with autoimmune-induced TD in clinical practice because these endocrine diseases are linked by the same pathophysiological mechanism.”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > TD and T1D
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The correlation between TSH and BMI could be mediated by leptin produced by adipose tissue because a positive correlation has been identified between serum leptin and serum TSH levels in individuals who are obese.TSH in turn can stimulate leptin secretion by human adipose tissue via TSH receptors that are expressed on adipocytes (, , ).”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Obesity
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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In the paper
“Both subclinical and overt hypothyroidism are frequently associated with weight gain, decreased thermogenesis, and metabolic rate (, ).”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Obesity
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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In the paper
“In fact, T can directly cross the blood-brain barrier, and the central administration of T activates the mTOR signaling pathway and is associated with increased expression of AgRP and NPY, as well as decreased POMC expression in hypothalamic ARC (, ).”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Effects of hypothalamic pituitary thyroid axis on appetite regulation
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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In the paper
“TH has insulin-antagonistic effects in the liver, whereas it acts synergically with insulin in the peripheral tissues.”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Central and Peripheral Effects of THs on the Regulation of b Cell Function, Glucose Tolerance, Hepatic Glucose Production, and Peripheral Glucose Utilization
What the sources say
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In the paper
“Isolated hyperthyrotropinemia is frequently observed in patients who are obese.It is a condition spontaneously reversible by losing weight without the necessity of specific treatment; in fact, it is usually associated with FT levels that are at the upper limit of the normal range ().”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Obesity
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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In the paper
“An increase of total cholesterol and its subfractions is a common finding in hypothyroidism, and a direct relationship between serum TSH and total cholesterol levels has been described ().”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Lipids, blood pressure, and nonalcoholic fatty liver disease
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“TH exerts profound effects on the regulation of glucose homeostasis and lipid metabolism.”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Central and Peripheral Effects of THs on the Regulation of b Cell Function, Glucose Tolerance, Hepatic Glucose Production, and Peripheral Glucose Utilization
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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In the paper
“TSH has also been shown to reduce food intake when injected centrally into rats and could be involved with the seasonal alterations in food intake and body weight that occur in some species (, ).”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Effects of hypothalamic pituitary thyroid axis on appetite regulation
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Insulin has anorectic effects in the central nervous system and its ICV administration reduces food intake and body weight () (Fig. ).Its anorectic effect involves insulin receptors on ARC neurons ().”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Effects of hypothalamic pituitary thyroid axis on appetite regulation
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Mitochondrial dysfunction can represent the common mechanism related to both DM and TD that can be aggravated by statins.”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Hypothyroidism and T2D
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In the paper
“THs modulate cholesterol synthesis, mobilization, and breakdown.In particular, they increase cholesterol synthesis via the rate-limiting enzyme -OHmethylglutaryl coenzyme A reductase and, in turn, stimulate its removal by enhancing the expression of low-density lipoprotein (LDL) receptors in the liver ().”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Lipids, blood pressure, and nonalcoholic fatty liver disease
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In the HUNT Study, among , euthyroid individuals, serum TSH levels within the euthyroid range were positively and significantly associated with total cholesterol, LDL-C, and triglycerides, with an inverse relationship between serum TSH and HDL-C ().”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Lipids, blood pressure, and nonalcoholic fatty liver disease
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In the paper
“A prothrombotic state and a proinflammatory state are usually associated with MetS, which is as an independent risk factor for CVDs and TD (, ).”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Underlying Mechanisms of the Association Between MetS in TD
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“T and noradreanaline increase UCP expression by twofold separately.On the contrary, when both agents are combined they induce a -fold expression of UCP ().”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Effects of TH on thermogenesis
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“T-treated rats have significantly lower plasma leptin levels compared with control rats; hypothalamic expression of NPY mRNA is increased fourfold, and hypothalamic POMC and CART mRNA are reduced by ~%, compared with control rats.”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Effects of hypothalamic pituitary thyroid axis on appetite regulation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“TH affects food intake, resting energy expenditure, and thermogenesis, and consequently metabolic alterations can develop in patients with TD.”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Underlying Mechanisms of the Association Between MetS in TD
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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In the paper
“A growing body of evidence suggests that hypothyroidism is a risk factor for incident chronic kidney disease, progression of chronic kidney disease , and higher death risk in kidney disease patients (, ).”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Prognosis of Patients With T2D and Associated TD: Long-Term Morbidity and Mortality
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In the paper
“Conversely, the combination of high serum TSH and thyroid autoimmunity in early pregnancy was associated with a fourfold increased risk for GMD (RR, .; % CI, . to .) and a threefold increased risk for low birth weight neonates (RR, .; % CI, . to .) after adjustment for several confounders ().”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Thyroid Dyfunction and Gestational Diabetes
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In the paper
“DM caused . million deaths in , with an excess relative risk of mortality, ranging from . to ., mainly attributable to cardiovascular causes (-).”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Prognosis of Patients With T2D and Associated TD: Long-Term Morbidity and Mortality
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Both MetS and hypothyroidism are independent risk factors for CVDs ().”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Association between MetS and TH deficiency
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, the authors concluded that SHypo is prevalent in patients with TD and may be responsible for a greater risk of diabetic complications such as DN, DR, PAD, and DPN, but not CHD ().”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Prognosis of Patients With T2D and Associated TD: Long-Term Morbidity and Mortality
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In the paper
“Higher TSH levels were also associated with higher triglycerides and lower HDL; furthermore, this relationship was stronger among individuals who were overweight (BMI .kg/m ) ().”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Lipids, blood pressure, and nonalcoholic fatty liver disease
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There are insufficient data to assess the specific tests for screening (TSH alone, TSH and TPO, or TSH and FT4), the exact interval of periodic screening, and the cost-benefit ratio.”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Screening of TD in patients with T2D
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Severe maternal hypothyroidism is associated with an increased risk of adverse pregnancy complications (fetal death, premature birth, low birth weight, pregnancy loss, and gestational hypertension) as well as detrimental effects on fetal neurocognitive development, leading to a lower intelligence quotient in the offspring (-).”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Thyroid Dyfunction and Gestational Diabetes
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The prevalence of GDM in pregnant women ranges from .% to %, with a wide difference according to country, screening strategy, and diagnostic criteria (, -).”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Thyroid Dyfunction and Gestational Diabetes
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“TD was observed in .% of women with TD in the first trimester and .% in the third trimester; the prevalent form of TD was subclinical or overt hypothyroidism ().”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Thyroid Dyfunction and Gestational Diabetes
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The incidence of TD during pregnancy in women with TD is threefold higher than in the general population, particularly in the first trimester of pregnancy and in the first year postpartum ().”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Thyroid Dyfunction and Gestational Diabetes
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“SHypo was associated with albuminuria in patients with TD, and an increased serum TSH was an independent risk factor for the presence of albuminuria ().”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Prognosis of Patients With T2D and Associated TD: Long-Term Morbidity and Mortality
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None of the sources cited for this claim have been checked yet.
In the paper
“Individual participant data meta-analyses reported that SHypo was associated with an increased risk for coronary heart disease (CHD) events and mortality () and heart failure (), especially in patients with serum TSH .mU/L.”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Prognosis of Patients With T2D and Associated TD: Long-Term Morbidity and Mortality
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The clinical presentation can vary from hyperthyroidism to hypothyroidism or both and is associated with a significant increased incidence of depression ().”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Risk of postpartum thyroiditis in patients with diabetes
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“A large meta-analysis reported that the presence of thyroid autoantibodies did not increase the risk of GDM in euthyroid pregnant women, and their positivity in the first trimester did not have a predictive value for the risk of GDM ().”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Thyroid Dyfunction and Gestational Diabetes
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Patients with DM have an increased risk of heart disease, stroke, heart failure, kidney disease, blindness, amputations, and neuropathy (-).”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Prognosis of Patients With T2D and Associated TD: Long-Term Morbidity and Mortality
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“All of these studies suggest that atherogenic dyslipidemia, insulin resistance, and hypertension can be linked with overt and subclinical hypothyroid states, and consequently TH deficiency is significantly associated with some components of MetS.”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Lipids, blood pressure, and nonalcoholic fatty liver disease
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“clinical symptoms of TD may be masked by a poor metabolic control, which is more frequent when TD develops”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Screening of TD in patients with T2D
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Euthyroid subjects with TSH values in the upper normal range (. to . mU/L) were more obese (BMI .kg/m ), had higher triglyceride levels, and had an increased likelihood of having MetS ().”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Association between MetS and TH deficiency
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“SHypo was associated with an OR of . (% CI, . to .) for the development of DN and was also responsible for an increased risk of cardiovascular events mediated by DN ().”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Prognosis of Patients With T2D and Associated TD: Long-Term Morbidity and Mortality
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Mild subclinical thyroid disease can progress at a low rate, suggesting a long-term screening program.”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Screening of TD in patients with T2D
What the sources say
- Not checked yetcites [3] Hollowell, 2002, Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III), J Clin Endocrinol Metab source
- Not checked yetcites [4] Cooper, 2012, Subclinical thyroid disease, Lancet source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Undetected thyroid disorders can compromise the metabolic control and amplify the risk of cardiovascular events.”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Screening of TD in patients with T2D
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These uncertainties do not allow us to adopt specific recommendations from the guidelines published by the major endocrine and diabetes societies”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Screening of TD in patients with T2D
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The screening of TD could prevent the high cardiovascular complications of T2D.”
§ Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders > Screening of TD in patients with T2D
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
The paper relies on this without support.
Insulin resistance is the main clinical and pathogenic feature of metabolic syndrome.
“Isulin resistance is the main clinical and pathogenic feature of this syndrome.”
The paper relies on this without support.
Human brown adipose tissue is more important in neonates than in adults.
“However, human BAT is considered more important in neonates than in the adults.”
The paper relies on this without support.
The prevalence of hypothyroidism in women of reproductive age is 2% to 3%.
“The prevalence of hypothyroidism in women during the reproductive age is % to %, and chronic autoimmune thyroiditis is the main cause of hypothyroidism during pregnancy.”
The paper relies on this without support.
Postpartum thyroiditis is caused by destructive autoimmune thyroiditis in the postpartum period, mediated by a rebound of cellular and humoral immunity.
“Postpartum thyroiditis (PPTD) is caused by a destructive autoimmune thyroiditis in the postpartum period, mediated by a rebound of both cellular and humoral immunity.”
The paper relies on this without support.
The cost-benefit ratio is favorable for screening thyroid dysfunction in type 1 diabetes.
“• The cost-benefit ratio is favorable for a screening of TD.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Furthermore, excess T3 leads to considerable impairment of the islet function, while physiological T3 treatment promotes beta-cell proliferation (57, 62).”
From The progression of secondary diabetes: A review of modeling studies (2022) · cites this paper as [57]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Changes in serum TSH are also associated with the incidence of T2DM, but the connection is merely significant in hypothyroidism (57).”
From The progression of secondary diabetes: A review of modeling studies (2022) · cites this paper as [57]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Thyroid dysfunction and diabetes mellitus are closely linked, and the liver is the main organ of glucose metabolism in the human (Biondi et al., 2019; Sridhar et al., 2014).”
From Exposure to per- and polyfluoroalkyl substances in early pregnancy, risk of gestational diabetes mellitus, potential pathways, and influencing factors in pregnant women: A nested case-control study (2023) · cites this paper as Biondi et al., 2019
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Moreover, T3 exerts profound effects on the proliferation of pancreatic islet cells and insulin secretion (57, 59).”
From The progression of secondary diabetes: A review of modeling studies (2022) · cites this paper as [57]
The cited source says what the claim attributes to it.
In the citing paper
“There are strong associations between diabetes mellitus and numerous concurrent health issues, such as osteoporosis, thyroid dysfunction, and abnormalities in iron metabolism (2–4).”
From Biological variation in serum thyroid, iron metabolism, and plasma bone metabolism biomarkers in patients with type 2 diabetes mellitus (2025) · cites this paper as [2]
The cited source says what the claim attributes to it.
In the citing paper
“There are strong associations between diabetes mellitus and numerous concurrent health issues, such as osteoporosis, thyroid dysfunction, and abnormalities in iron metabolism (2–4).”
From Biological variation in serum thyroid, iron metabolism, and plasma bone metabolism biomarkers in patients with type 2 diabetes mellitus (2025) · cites this paper as [2]
The cited source says what the claim attributes to it.
In the citing paper
“Furthermore, excess T3 leads to considerable impairment of the islet function, while physiological T3 treatment promotes beta-cell proliferation (57, 62).”
From The progression of secondary diabetes: A review of modeling studies (2022) · cites this paper as [57]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“There are strong associations between diabetes mellitus and numerous concurrent health issues, such as osteoporosis, thyroid dysfunction, and abnormalities in iron metabolism (2–4).”
From Biological variation in serum thyroid, iron metabolism, and plasma bone metabolism biomarkers in patients with type 2 diabetes mellitus (2025) · cites this paper as [2]
Experimental — accuracy not yet measured
Citations
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Metadata
- Authors
- Biondi, B., Kahaly, G. J., & Robertson, R. P.
- Affiliations
- Federico II University Hospital (IT)
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- University of Washington (US)
- Corresponding author
- Biondi, Bernadette
- Venue
- Endocrine Reviews
- Publisher
- The Endocrine Society
- Published
- 2019-01-14
- Volume
- 40
- Issue
- 3
- Pages
- 789-824
- ISSN
- 0163-769X (ISSN-L)
- 1945-7189
- PMC
- PMC6507635
- OpenAlex
- W2909632761
- Semantic Scholar
- 5611ced84cb98c912f119fd45af52bec095d4953
- Cited by
- 598
- References
- 410
- Citations by year
- 2026: 81 · 2025: 105 · 2024: 120 · 2023: 107 · 2022: 98 · 2021: 50 · 2020: 28 · 2019: 9
- FWCI
- 7.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrine Reviews (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (NIDDK RO-1 38325-35)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- thyroid dysfunction, diabetes mellitus, type 1 diabetes, type 2 diabetes, subclinical hypothyroidism, overt hypothyroidism, metabolic syndrome, thyroid hormone regulation, glucose metabolism, lipid metabolism, adipose tissue, pancreatic beta cells, skeletal muscle, autoimmune thyroid disease, susceptibility genes, antidiabetic drugs, treatment algorithm
- MeSH terms
- Animals, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Humans, Hypothyroidism, Thyroid Diseases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-08, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-08 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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