Correlation Between Hypothyroidism and Insulin Resistance
Hypothyroidism is strongly associated with increased insulin resistance, with the highest insulin resistance observed in overt hypothyroidism, followed by subclinical hypothyroidism, and lowest in euthyroid individuals. 1
Magnitude of Association
The relationship between hypothyroid disorders and insulin resistance demonstrates a clear dose-response pattern:
Overt hypothyroidism shows the strongest association, with mean HOMA-IR values of 3.22 ± 2.69 compared to 0.79 ± 0.58 in euthyroid individuals (p<0.001), representing approximately a 4-fold increase in insulin resistance 1
Subclinical hypothyroidism demonstrates intermediate effects, with mean HOMA-IR of 2.03 ± 0.95 versus 1.05 ± 0.45 in euthyroid controls (p<0.0001), representing roughly a 2-fold increase 2
TSH levels correlate positively with insulin resistance, showing moderate correlation with HOMA-IR (r=0.945, p<0.001 in hypothyroid patients) 1 and with fasting insulin levels (r=0.43, p=0.03) 2
Mechanistic Predictors
The FT3/FT4 ratio emerges as the strongest predictor of insulin resistance, more so than TSH alone:
FT3/FT4 ratio is the only significant independent predictor of HOMA-IR (linear coefficient = 5.26, p=0.027) and insulin levels (linear coefficient = 18.01, p=0.023) in both euthyroid and hypothyroid adults 3
FT3 shows strong correlations with insulin resistance markers (r=0.205, p<0.001 for insulin; r=0.181, p<0.001 for HOMA-IR) 3
FT3 levels negatively correlate with insulin (r=-0.5, p=0.004) and HOMA-IR (r=-0.38, p=0.04) in subclinical hypothyroidism 2
Clinical Implications for Metabolic Risk
The insulin resistance associated with hypothyroidism translates into tangible cardiovascular and metabolic risks:
Dyslipidemia accompanies the insulin resistance, with significantly elevated cholesterol, LDL, VLDL, and triglycerides, while HDL is decreased in hypothyroid patients 4
TSH correlates significantly with cholesterol and LDL in both clinical and subclinical hypothyroidism 4
Insulin resistance in childhood predicts future cardiovascular risk, with fasting insulin levels in children predicting blood pressure elevation years later 5
Important Caveats and Conflicting Evidence
One study found no association between subclinical hypothyroidism and insulin resistance in Romanian adult women after adjusting for metabolic syndrome components, suggesting that coexisting metabolic syndrome elements may be more important determinants of insulin resistance than thyroid dysfunction per se 6. This highlights that:
Metabolic syndrome may confound the relationship, as obesity independently drives insulin resistance regardless of thyroid status 5
The association may be bidirectional or share common underlying mechanisms rather than representing pure causation 5
Treatment Considerations
When treating hypothyroidism in patients with diabetes or insulin resistance:
Levothyroxine therapy may worsen glycemic control and increase antidiabetic agent or insulin requirements, according to FDA labeling 7
Careful monitoring of glycemic control is essential, especially when thyroid therapy is started, changed, or discontinued 7
Cognitive symptoms from hypothyroidism may take several weeks to improve after biochemical normalization, even as insulin resistance improves 8
Practical Clinical Approach
When evaluating the metabolic impact of hypothyroidism:
Measure both TSH and FT3/FT4 ratio to best assess insulin resistance risk, as the FT3/FT4 ratio provides superior predictive value compared to TSH alone 3
Screen for insulin resistance using HOMA-IR in all hypothyroid patients, particularly those with TSH >10 mIU/L 2
Assess lipid profiles concurrently, as the dyslipidemia associated with hypothyroidism compounds cardiovascular risk independently 4
Consider that visceral adiposity amplifies the relationship between thyroid dysfunction and insulin resistance, with waist circumference being a stronger predictor than BMI 5