Risk of Thyroid Cancer in People With Type 1 Diabetes by Autoimmune Thyroid Diseases and Tumor Histology.

Context: Thyroid cancer is the most common endocrine cancer, but little is known about it in type 1 diabetes (T1D) and its potential association with autoimmune diseases. Objective: This study aims to assess the risk of thyroid cancer in adults with long-term T1D compared to individuals without diabetes and the proposed association of thyroid autoimmune diseases with thyroid cancer. Methods: The study included 4758 individuals with T1D participating in the Finnish Diabetic Nephropathy Study and 12 710 controls. Thyroid cancers were obtained from the Finnish Care Registers for Health Care. Results: 27 (0.57%) individuals with T1D had thyroid cancer compared to 27 (0.21%) in the controls (standardized incidence ratio 2.43; 95% confidence interval 1.59-3.56). The absolute increase in incidence was modest, with a 0.36%-unit rise. This translates to 17 additional cases among 4710 individuals with T1D. Cancer type was papillary in 81.5% of individuals with T1D and 88.9% of the controls; the rest were follicular. In T1D the distribution of hypothyreosis was similar between those with (n = 5, 18.5%) and without (18.1%) cancer, but hyperthyreosis was diagnosed more often with thyroid cancer (n = 3, 11.1%) than without (2.3%, P = .003). None of the thyroid cancers were invasive or had metastatic characteristics. Conclusion: Although there is an excess risk of thyroid cancer, it is only marginally increased (0.36%-unit) in individuals with T1D compared to control individuals and was not associated with increased morbidity or mortality. An overdiagnosis effect due to regular health care contacts is the most likely explanation for the higher risk.

Incidence and risk factors for cancer in people with type 1 diabetes, stratified by stages of diabetic kidney disease: a nationwide Finnish cohort study.

Background: Individuals with type 1 diabetes (T1D) have been reported to have increased overall risk of cancer. In addition, individuals with a kidney transplant/transplantation (KT) have markedly increased cancer risk due to chronic use of immunosuppressive agents. However, it has not been elucidated whether the observed excess cancer risk is related to KT or whether diabetic kidney disease (DKD) per se is a risk factor for cancer in individuals with T1D. Methods: The study included 5035 individuals from the Finnish Diabetic Nephropathy Study (FinnDiane) and 14,061 control individuals without diabetes. We assessed the standardized incidence ratios (SIRs) for cancers in individuals with T1D compared to controls according to DKD status. Cox regression analyses were used to identify potential risk factors for cancer in individuals with type 1 diabetes. Findings: The SIR for overall cancer for all participants was 1.14 (1.05-1.24), for participants without KT 0.92 (0.83-1.01) and for participants with KT 4.78 (4.02-5.64). Participants without KT had in fact a reduced risk of prostate cancer with a SIR of 0.54 (0.37-0.76), cancer of urinary organs 0.41 (0.21-0.73) and respiratory and intrathoracic organs, 0.62 (0.38-0.97). Participants with KT had on the contrary an increased risk of non-melanoma skin cancer, SIR 14.50 (10.99-18.86), cancer in the lymphoid and hematopoietic tissue 5.38 (2.99-8.96), mouth or pharynx 5.13 (2.08-10.66), melanoma 5.12 [2.38-9.72]) and respiratory and intrathoracic organs 2.77 (1.21-5.49). The risk of thyroid cancer was increased both in participants without KT, SIR 2.14 (1.39-3.16) and with KT 5.30 (1.68-12.78). Interpretation: The excess overall cancer risk in individuals with type 1 diabetes is only seen in KT recipients and in thyroid cancer. The individuals without KT seem to have a decreased risk of some forms of cancer. Funding: Folkhälsan Research Foundation, Academy of Finland [316664], Wilhelm and Else Stockmann Foundation, Liv och Hälsa Society, Novo Nordisk Foundation [NNF OC0013659], Finnish Foundation for Cardiovascular Research, Finnish Diabetes Research Foundation, Medical Society of Finland, Sigrid Jusélius Foundation, and Helsinki University Hospital Research Funds [TYH2018207 and TYH 2020305].

The Long-Term Incidence of Hospitalization for Ketoacidosis in Adults with Established T1D-A Prospective Cohort Study.

CONTEXT: The long-term natural history of diabetic ketoacidosis (DKA) and its risk factors are poorly understood. OBJECTIVE: To determine the long-term incidence and predictors of DKA in adults with longstanding type 1 diabetes (T1D). DESIGN: All hospitalizations and deaths due to DKA between 1996 and 2016 were identified in 4758 adults with T1D from the Finnish Diabetic Nephropathy Study (FinnDiane), and a cohort of 16 224 adults with T1D from the Finnish general population. RESULTS: Between 1996 and 2015, there were 1228 DKA events in the FinnDiane participants (1.4/100 person-years) and 4914 DKA events (1.8/100 person-years) in adults with T1D from the general population. The majority were hospitalized only once. There was a modest increase in the frequency of DKA in the FinnDiane over the follow-up (~2.4%/year [95% CI, 0.3-4.5%]; P = 0.03). Predictors of DKA were glucose control, CSII, smoking and alcohol consumption, and raised high-density lipoprotein cholesterol and triacylglycerides. Diabetic nephropathy and renal impairment were associated with DKA; patients with end-stage renal disease, macroalbuminuria, and microalbuminuria had 2.09-fol (95% CI, 1.40-3.12), 1.65-fold (95% CI, 1.23-2.19), and 0.87-fold (95% CI, 0.61-1.24) risk of DKA compared with patients with normal albumin excretion rate, respectively. Patients with an estimated glomerular filtration rate <60 mL/min/1.73 m2 were also more likely to be hospitalized for DKA (HR 1.71 [95% CI, 1.26-2.67]). CONCLUSIONS: DKA remains a common cause of hospitalization in individuals with longstanding T1D. These data suggest that the goal to use SGLT2 inhibitors for their vasculo- and renoprotective actions may be problematic, as those most likely to benefit may also have the highest risk for DKA.

Dose-dependent effect of smoking on risk of coronary heart disease, heart failure and stroke in individuals with type 1 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to assess the potential dose-dependent effects of smoking on the risk of CHD, heart failure and stroke in individuals with type 1 diabetes. METHODS: The study included 4506 individuals with type 1 diabetes who were participating in the Finnish Diabetic Nephropathy (FinnDiane) study. Intensity of smoking was estimated by packs per day and cumulative smoking by pack-years. Cox regression analyses were used to estimate the risk of incident CHD, heart failure or stroke during follow-up. RESULTS: One pack per day significantly increased the risk of incident CHD in current smokers compared with never smokers (HR 1.45 [95% CI 1.15, 1.84]), after adjustment for age, sex, HbA1c, hypertension, duration of diabetes and BMI. The risk of CHD in former smokers was similar to the risk in never smokers. The risk of incident heart failure was 1.43 (95% CI 1.03, 1.97) in current smokers per one pack per day and 1.37 (95% CI 1.05, 1.77) in former smokers, while the risk of incident stroke was 1.70 (95% CI 1.26, 2.29) and 1.49 (95% CI 1.14, 1.93), respectively. After further adjustments for lipids, however, the difference in the risk of heart failure in current and former smokers was no longer significant. Cumulative smoking data were similar to smoking intensity data. CONCLUSIONS/INTERPRETATION: There is a dose-dependent association between smoking and cardiovascular disease in individuals with type 1 diabetes. In men in particular, the risk of incident stroke remains high even after smoking cessation and is increased in current and former smokers independently of other risk factors.

Excess Mortality in Patients With Type 1 Diabetes Without Albuminuria-Separating the Contribution of Early and Late Risks.

OBJECTIVE: The current study investigated whether the risk of mortality in patients with type 1 diabetes without any signs of albuminuria is different than in the general population and matched control subjects without diabetes. RESEARCH DESIGN AND METHODS: We studied a nationwide, population-based Finnish register of 10,737 patients diagnosed with type 1 diabetes during 1980-2005 and followed for 10 years and 2,544 adults with long-standing diabetes drawn from the Finnish Diabetic Nephropathy Study (FinnDiane). Mortality was compared with the general Finnish population and 6,655 control subjects without diabetes. RESULTS: The standardized mortality ratio (SMR) was increased during the first 10 years after the diagnosis (2.58 [95% CI 2.07-3.18], P < 0.001). Mortality in adults with long-standing diabetes, but without albuminuria, was no different from that of the general population (1.02 [0.84-1.22], P = 0.83). However, it was higher compared with that of control subjects without diabetes (1.33 [1.06-1.66], P = 0.01). Excess mortality was largely due to acute diabetes complications and ischemic heart disease, which remained more than fourfold higher (mortality rate ratio 4.34 [2.49-7.57]) in adults with type 1 diabetes than in control subjects without diabetes, despite the absence of albuminuria. By contrast, deaths due to alcohol and drugs were reduced in adults with type 1 diabetes (P = 0.007), especially in men. CONCLUSIONS: Excess mortality in type 1 diabetes is the result of its complications. Acute complications drive an increased SMR in the first years. In individuals who remain free of albuminuria, mortality due to ischemic heart disease is still four times higher, and acute complications also occur.

Smoking and progression of diabetic nephropathy in patients with type 1 diabetes.

AIMS: To evaluate the effect of cumulative smoking on the development of diabetic nephropathy. METHODS: Study included 3613 patients with type 1 diabetes, participating in the Finnish Diabetic Nephropathy Study. The 12-year cumulative risk of microalbuminuria, macroalbuminuria and end-stage renal disease (ESRD) was estimated for current, ex- and nonsmokers. Cox regression analyses, with multivariable adjustments for other risk factors for diabetic nephropathy, were used to evaluate the risk at different stages of diabetic nephropathy based on the cumulative amount of smoking in pack-years. RESULTS: The 12-year cumulative risk of microalbuminuria was 18.9 % (95 % CI 14.6-23.0, P < 0.0001) for current smokers and 15.1 % (10.3-19.6, P = 0.087) for ex-smokers, compared with 10.0 % (7.8-12.1) for nonsmokers. The corresponding risks of macroalbuminuria were 14.4 % (95 % CI 10.8-17.9, P < 0.0001), 6.1 % (3.5-8.6, P = 0.082) and 4.7 % (3.0-6.4), respectively. The 12-year cumulative risk of ESRD was 10.3 % (95 % CI 8.4-12.4, P < 0.0001) for current smokers and 10.0 % (7.9-12.3, P < 0.0001) for ex-smokers, compared with 5.6 % (4.6-6.7) for nonsmokers. In the current smokers, one pack-year increased the risk of macroalbuminuria with a HR of 1.025 (1.010-1.041) and the risk of ESRD with a HR of 1.014 (1.001-1.026) compared with nonsmokers, in the fully adjusted model. In the ex-smokers, the risk of macroalbuminuria and ESRD was no different from the risk in nonsmokers after multivariable adjustment. CONCLUSIONS: Current smoking is a risk factor for the progression of diabetic nephropathy and the risk increases with the increasing dose of smoking. Ex-smokers seem to carry a similar risk of progression of diabetic nephropathy as nonsmokers.

Different lipid variables predict incident coronary artery disease in patients with type 1 diabetes with or without diabetic nephropathy: the FinnDiane study.

OBJECTIVE: To study the ability of lipid variables to predict incident coronary artery disease (CAD) events in patients with type 1 diabetes at different stages of nephropathy. RESEARCH DESIGN AND METHODS: Patients (n = 3,520) with type 1 diabetes and available lipid profiles participating in the Finnish Diabetic Nephropathy Study (FinnDiane) were included in the study. During a follow-up period of 10.2 years (8.6-12.0), 310 patients suffered an incident CAD event. RESULTS: Apolipoprotein B (ApoB)/ApoA-I ratio was the strongest predictor of CAD in normoalbuminuric patients (hazard ratio 1.43 [95% CI 1.17-1.76] per one SD increase), and ApoB was the strongest in macroalbuminuric patients (1.47 [1.19-1.81]). Similar results were seen when patients were stratified by sex or glycemic control. LDL cholesterol was a poor predictor of CAD in women, normoalbuminuric patients, and patients with HbA1c below the median (8.3%, 67 mmol/L). The current recommended triglyceride cutoff of 1.7 mmol/L failed to predict CAD in normoalbuminuric patients, whereas the cohort median 0.94 mmol/L predicted incident CAD events. CONCLUSIONS: In patients with type 1 diabetes, the predictive ability of the lipid variables differed substantially depending on the patient's sex, renal status, and glycemic control. In normoalbuminuric patients, the ratios of atherogenic and antiatherogenic lipoproteins and lipids were the strongest predictors of an incident CAD event, whereas in macroalbuminuric patients, no added benefit was gained from the ratios. Current treatment recommendations may need to be revised to capture residual CAD risk in patients with type 1 diabetes.