Resistant hypertension and risk of adverse events in individuals with type 1 diabetes: A nationwide prospective study

Objectives. To estimate the risk of diabetic nephropathy (DN) progression, incident coronary heart disease (CHD) and stroke, and all-cause mortality associated with resistant hypertension (RH) in individuals with type 1 diabetes stratified by stages of DN, renal function and sex. Research Design and Methods This prospective study included a nationally representative cohort of individuals with type 1 diabetes from the Finnish Diabetic Nephropathy Study who had purchases of antihypertensive drugs at (±6 months) baseline visit (1995–2008). Individuals (N=1,103) were divided into three groups: (a) RH, (b) uncontrolled BP, but no RH and (c) controlled BP. DN progression, cardiovascular events and deaths were identified from the individuals’ healthcare records and national registries, until 31 December 2015. Results At baseline 18.7% of the participants had RH, while 23.4% had controlled BP. After full adjustments for clinical confounders, RH was associated with increased risk of DN progression (HR 1.95 [95% CI 1.37, 2.79], p=0.0002), while no differences were observed in those with no RH (1.05 [0.76, 1.44], p=0.8), compared with those who had controlled BP. The risk of incident CHD, incident stroke and all-cause mortality was higher in individuals with RH compared with those who had controlled BP, but not beyond albuminuria and reduced kidney function. Notably, in those with normo- and microalbuminuria the risk of stroke remained higher in the RH compared to controlled BP group (3.49 [81.20, 10.15], p=0.02). Conclusion Our findings highlight importance to identify and provide diagnostic and therapeutic counseling to these very high risk individuals with RH.

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Resistant hypertension and risk of adverse events in individuals with type 1 diabetes: A nationwide prospective study

10.2337/figshare.12137604.v2 ◽

2020 ◽

Author(s):

Raija Lithovius ◽

Valma Harjutsalo ◽

Stefan Mutter ◽

Daniel Gordin ◽

Carol Forsblom ◽

...

Keyword(s):

Type 1 Diabetes ◽

Diabetic Nephropathy ◽

Prospective Study ◽

Resistant Hypertension ◽

Antihypertensive Drugs ◽

Increased Risk ◽

All Cause Mortality ◽

Nationally Representative ◽

Reduced Kidney Function

Objectives. To estimate the risk of diabetic nephropathy (DN) progression, incident coronary heart disease (CHD) and stroke, and all-cause mortality associated with resistant hypertension (RH) in individuals with type 1 diabetes stratified by stages of DN, renal function and sex. Research Design and Methods This prospective study included a nationally representative cohort of individuals with type 1 diabetes from the Finnish Diabetic Nephropathy Study who had purchases of antihypertensive drugs at (±6 months) baseline visit (1995–2008). Individuals (N=1,103) were divided into three groups: (a) RH, (b) uncontrolled BP, but no RH and (c) controlled BP. DN progression, cardiovascular events and deaths were identified from the individuals’ healthcare records and national registries, until 31 December 2015. Results At baseline 18.7% of the participants had RH, while 23.4% had controlled BP. After full adjustments for clinical confounders, RH was associated with increased risk of DN progression (HR 1.95 [95% CI 1.37, 2.79], p=0.0002), while no differences were observed in those with no RH (1.05 [0.76, 1.44], p=0.8), compared with those who had controlled BP. The risk of incident CHD, incident stroke and all-cause mortality was higher in individuals with RH compared with those who had controlled BP, but not beyond albuminuria and reduced kidney function. Notably, in those with normo- and microalbuminuria the risk of stroke remained higher in the RH compared to controlled BP group (3.49 [81.20, 10.15], p=0.02). Conclusion Our findings highlight importance to identify and provide diagnostic and therapeutic counseling to these very high risk individuals with RH.

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Resistant Hypertension and Risk of Adverse Events in Individuals With Type 1 Diabetes: A Nationwide Prospective Study

Diabetes Care ◽

10.2337/dc20-0170 ◽

2020 ◽

Vol 43 (8) ◽

pp. 1885-1892

Author(s):

Raija Lithovius ◽

Valma Harjutsalo ◽

Stefan Mutter ◽

Daniel Gordin ◽

Carol Forsblom ◽

...

Keyword(s):

Type 1 Diabetes ◽

Adverse Events ◽

Prospective Study ◽

Resistant Hypertension

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The V16A polymorphism in SOD2 is associated with increased risk of diabetic nephropathy and cardiovascular disease in type 1 diabetes

Diabetologia ◽

10.1007/s00125-009-1550-1 ◽

2009 ◽

Vol 52 (12) ◽

pp. 2590-2593 ◽

Cited By ~ 25

Author(s):

A. Möllsten ◽

A. Jorsal ◽

M. Lajer ◽

N. Vionnet ◽

L. Tarnow

Keyword(s):

Cardiovascular Disease ◽

Type 1 Diabetes ◽

Diabetic Nephropathy ◽

Increased Risk

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Antihypertensive Treatment and Resistant Hypertension in Patients With Type 1 Diabetes by Stages of Diabetic Nephropathy

Diabetes Care ◽

10.2337/dc13-2023 ◽

2013 ◽

Vol 37 (3) ◽

pp. 709-717 ◽

Cited By ~ 10

Author(s):

Raija Lithovius ◽

Valma Harjutsalo ◽

Carol Forsblom ◽

Markku Saraheimo ◽

Per-Henrik Groop ◽

...

Keyword(s):

Type 1 Diabetes ◽

Diabetic Nephropathy ◽

Resistant Hypertension ◽

Antihypertensive Treatment

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Depression is associated with progression of diabetic nephropathy in type 1 diabetes

10.2337/figshare.13073387 ◽

2020 ◽

Author(s):

Aila J. Ahola ◽

Valma Harjutsalo ◽

Carol Forsblom ◽

François Pouwer ◽

Per-Henrik Groop ◽

...

Keyword(s):

Type 1 Diabetes ◽

Diabetic Nephropathy ◽

Renal Disease ◽

End Stage Renal Disease ◽

Symptoms Of Depression ◽

Increased Risk ◽

Stage Renal Disease ◽

End Stage

OBJECTIVE To investigate the relationship between depression and diabetic nephropathy progression in type 1 diabetes. RESEARCH DESIGN AND METHODS Data from 3730 participants without end-stage renal disease at baseline, participating in the Finnish Diabetic Nephropathy Study, were included. Depression was assessed in three ways. Depression diagnoses were obtained from the Finnish Care Register for Health Care. Antidepressant agent purchase data were obtained from the Drug Prescription Register. Symptoms of depression were assessed using the Beck Depression Inventory (BDI). Based on their urinary albumin excretion rate (AER) participants were classified into those with normal AER, microalbuminuria, and macroalbuminuria. Progression from normal AER to either microalbuminuria, macroalbuminuria, or end-stage renal disease; or from microalbuminuria to macroalbuminuria or ESRD; or from macroalbuminuria to ESRD, during the follow-up period was investigated. RESULTS Over a mean follow-up period of 9.6 years, renal status deteriorated in 18.4% of the participants. Diagnosed depression and antidepressant purchases before baseline were associated with 53% and 32% increased risk of diabetic nephropathy progression, respectively. Diagnosed depression assessed during follow-up remained associated with increased risk of disease progression (32%). BDI-derived symptoms of depression showed no association with the progression, but the total number of antidepressant purchases modestly reduced the risk [0.989 (0.982–0.997), P=0.008]. Dividing the sample based on median age, the observations followed those seen in the whole group. However, symptoms of depression additionally predicted progression in those ≤36.5 years. CONCLUSIONS Diagnosed depression and antidepressant purchases are associated with the progression of diabetic nephropathy in type 1 diabetes. Whether successful treatment of depression reduces the risk needs to be determined.

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Osteopontin Is a Strong Predictor of Incipient Diabetic Nephropathy, Cardiovascular Disease, and All-Cause Mortality in Patients With Type 1 Diabetes

Diabetes Care ◽

10.2337/dc14-0065 ◽

2014 ◽

Vol 37 (9) ◽

pp. 2593-2600 ◽

Cited By ~ 35

Author(s):

Daniel Gordin ◽

Carol Forsblom ◽

Nicolae M. Panduru ◽

Merlin C. Thomas ◽

Mette Bjerre ◽

...

Keyword(s):

Cardiovascular Disease ◽

Type 1 Diabetes ◽

Diabetic Nephropathy ◽

Strong Predictor ◽

All Cause Mortality ◽

Incipient Diabetic Nephropathy

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The impact of central obesity on the risk of hospitalization or death due to heart failure in type 1 diabetes: a 16-year cohort study

Cardiovascular Diabetology ◽

10.1186/s12933-021-01340-4 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Erika B. Parente ◽

Valma Harjutsalo ◽

Carol Forsblom ◽

Per-Henrik Groop ◽

Keyword(s):

Heart Failure ◽

Type 1 Diabetes ◽

Diabetic Nephropathy ◽

Central Obesity ◽

Cox Regression ◽

General Obesity ◽

Increased Risk ◽

Incident Cases ◽

The Impact

Abstract Background Obesity and type 2 diabetes are well-known risk factors for heart failure (HF). Although obesity has increased in type 1 diabetes, studies regarding HF in this population are scarce. Therefore, we investigated the impact of body fat distribution on the risk of HF hospitalization or death in adults with type 1 diabetes at different stages of diabetic nephropathy (DN). Methods From 5401 adults with type 1 diabetes in the Finnish Diabetic Nephropathy Study, 4668 were included in this analysis. The outcome was HF hospitalization or death identified from the Finnish Care Register for Health Care or the Causes of Death Register until the end of 2017. DN was based on urinary albumin excretion rate. A body mass index (BMI) ≥ 30 kg/m2 defined general obesity, whilst WHtR ≥ 0.5 central obesity. Multivariable Cox regression was used to explore the associations between central obesity, general obesity and the outcome. Then, subgroup analyses were performed by DN stages. Z statistic was used for ranking the association. Results During a median follow-up of 16.4 (IQR 12.4–18.5) years, 323 incident cases occurred. From 308 hospitalizations due to HF, 35 resulted in death. Further 15 deaths occurred without previous hospitalization. The WHtR showed a stronger association with the outcome [HR 1.51, 95% CI (1.26–1.81), z = 4.40] than BMI [HR 1.05, 95% CI (1.01–1.08), z = 2.71]. HbA1c [HR 1.35, 95% CI (1.24–1.46), z = 7.19] was the most relevant modifiable risk factor for the outcome whereas WHtR was the third. Individuals with microalbuminuria but no central obesity had a similar risk of the outcome as those with normoalbuminuria. General obesity was associated with the outcome only at the macroalbuminuria stage. Conclusions Central obesity associates with an increased risk of heart failure hospitalization or death in adults with type 1 diabetes, and WHtR may be a clinically useful screening tool.

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Lipidomic analysis reveals sphingomyelin and phosphatidylcholine species associated with renal impairment and all-cause mortality in type 1 diabetes

Scientific Reports ◽

10.1038/s41598-019-52916-w ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 8

Author(s):

Nete Tofte ◽

Tommi Suvitaival ◽

Linda Ahonen ◽

Signe A. Winther ◽

Simone Theilade ◽

...

Keyword(s):

Type 1 Diabetes ◽

Diabetic Nephropathy ◽

Lower Risk ◽

Multiple Testing ◽

Multiple Testing Correction ◽

Cross Sectional ◽

Lipid Species ◽

All Cause Mortality

Abstract There is an urgent need for a better molecular understanding of the pathophysiology underlying development and progression of diabetic nephropathy. The aim of the current study was to identify novel associations between serum lipidomics and diabetic nephropathy. Non-targeted serum lipidomic analyses were performed with mass spectrometry in 669 individuals with type 1 diabetes. Cross-sectional associations of lipid species with estimated glomerular filtration rate (eGFR) and urinary albumin excretion were assessed. Moreover, associations with register-based longitudinal follow-up for progression to a combined renal endpoint including ≥30% decline in eGFR, ESRD and all-cause mortality were evaluated. Median follow-up time was 5.0–6.4 years. Adjustments included traditional risk factors and multiple testing correction. In total, 106 lipid species were identified. Primarily, alkyl-acyl phosphatidylcholines, triglycerides and sphingomyelins demonstrated cross-sectional associations with eGFR and macroalbuminuria. In longitudinal analyses, thirteen lipid species were associated with the slope of eGFR or albuminuria. Of these lipids, phosphatidylcholine and sphingomyelin species, PC(O-34:2), PC(O-34:3), SM(d18:1/24:0), SM(d40:1) and SM(d41:1), were associated with lower risk of the combined renal endpoint. PC(O-34:3), SM(d40:1) and SM(d41:1) were associated with lower risk of all-cause mortality while an SM(d18:1/24:0) was associated with lower risk of albuminuria group progression. We report distinct associations between lipid species and risk of renal outcomes in type 1 diabetes, independent of traditional markers of kidney function.

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