patients with type 1 diabetes consuming alcoholic spirits have an increased risk of microvascular...

Research: Epidemiology

Patients with Type 1 diabetes consuming alcoholic spirits

have an increased risk of microvascular complications

V. Harjutsalo1,2,3,*, M. Feodoroff1,2,*, C. Forsblom1,2 and P.-H. Groop1,2,4 on behalf of theFinnDiane Study Group

1Folkh€alsan Institute of Genetics, Folkh€alsan Research Center, Biomedicum Helsinki, University of Helsinki, 2Division of Nephrology, Department of Medicine,

Helsinki University Central Hospital, 3National Institute for Health and Welfare, Diabetes Prevention Unit, Helsinki, Finland and 4The Baker IDI Heart and Diabetes

Institute, Melbourne, Vic., Australia

Accepted 12 August 2013

Abstract

Aims Our aim was to evaluate the effect of the amount of alcohol consumption and the type of beverage on the risk of

diabetic nephropathy and severe diabetic retinopathy.

Methods The alcohol consumption data were available from 3608 patients with Type 1 diabetes participating in the

Finnish Diabetic Nephropathy Study (FinnDiane). We assessed the cross-sectional association between alcohol

consumption and diabetic nephropathy as well as retinopathy. Patients were divided into different groups according to

the amount of alcohol and the type of beverage they were consuming.

Results In the multivariate analysis, the odds ratio for nephropathy was 1.39 (95% CI 1.05–1.84) for abstainers and2.44 (95% CI 1.49–3.99) for former users compared with light consumers. The results were similar in retinopathy, with

an odds ratio of 1.42 (95% CI 1.11–1.82) for abstainers and 1.73 (95% CI 1.07–2.79) for former users. No difference

between light consumers and moderate or heavy consumers was observed. Compared with wine drinkers, men

consuming mostly alcoholic spirits had a higher risk of nephropathy with an odds ratio of 2.80 (95% CI 1.15–6.81). Inwomen, there was no difference in the risk of nephropathy between the different beverage types. Alcoholic spirit

consumers had a higher risk of retinopathy with an odds ratio of 2.32 (95% CI 1.35–4.00). There was no difference

between wine and beer consumers.

Conclusions Alcoholic spirit drinkers carry a higher risk of nephropathy and severe retinopathy compared with wine

drinkers. Lifelong abstainers and former users of alcohol have a higher risk of nephropathy and severe retinopathy

compared with light consumers.

Diabet. Med. 31, 156–164 (2014)

Introduction

It is widely recognized that light-to-moderate alcohol con-

sumption shows beneficial effects on the risk of macrovas-

cular diseases, such as coronary heart disease and

non-haemorrhagic stroke. However, the potential associa-

tion between alcohol consumption and microvascular disease

such as diabetic nephropathy and retinopathy is still unclear

as there are only a few studies addressing this issue and most

of them do not focus on Type 1 diabetes.

The EURODIAB study reported a lower risk of diabetic

nephropathy and retinopathy in patients with Type 1

diabetes consuming moderate amounts of alcohol (30–70 g

per week), compared with abstainers and heavy drinkers [1].

In the other retinopathy studies, the results have been

contradictory [2–5]. These studies are, however, relatively

old and may not necessarily be representative of more recent

consumption behaviour. Furthermore, sample sizes were

small and the definition of retinopathy a mixture of back-

ground and proliferative retinopathy. Therefore, the associ-

ation between alcohol consumption and retinopathy is still

unresolved, as also pointed out by a recent review of the

effects of alcohol consumption on various eye diseases [6].

There are also some other important limitations in the

previous studies. Many of them did not differentiate between

former drinkers and lifelong abstainers in the analyses. It is

also of note that in the previous studies men and womenCorrespondence to: Per-Henrik Groop. E-mail: [email protected]

*These authors contributed equally to this article

156ª 2013 The Authors.

Diabetic Medicine ª 2013 Diabetes UK

DIABETICMedicine

DOI: 10.1111/dme.12307

were categorized using the same consuming strata, although

it is well known that alcohol affects men and women

differently [7].

Moreover, it is not known if the type of beverage has

different effects on the risk of diabetic microvascular

complications. Finally, although alcohol intake is heavily

related to smoking, the effect of alcohol has predominantly

been analysed without taking smoking into account. Given

the many contradictions and limitations associated with the

studies on this topic, we studied the association between

alcohol consumption and risk of diabetic nephropathy and

severe diabetic retinopathy in a large nationwide population

of 3608 patients with Type 1 diabetes representing a more

recent alcohol consumption pattern.

Subjects and methods

The data for the analyses presented are derived from the

Finnish Diabetic Nephropathy Study (FinnDiane). FinnDiane

is a nationwide, comprehensive multi-centre study, with the

aim to identify genetic and environmental risk factors for

diabetic complications, with special emphasis on diabetic

nephropathy in patients with Type 1 diabetes. A detailed

description of the FinnDiane recruitment protocol has

previously been presented [8].

Details on the clinical characteristics of the patients,

including age at diagnosis of diabetes, history of laser

treatment, presence of microalbuminuria, macroalbuminuria

or end-stage renal disease (dialysis or kidney transplanta-

tion), were obtained from the medical files by the attending

physician using a standardized questionnaire. In the present

study, the diagnosis of diabetic nephropathy was defined as

macroalbuminuria (albumin excretion rate > 200 lg/min or

> 300 mg/24 h) or end-stage renal disease and severe

diabetic retinopathy as a history of laser photocoagulation.

Patients were divided in to six groups according to their

social class.

Accuracy of the data on lipid-lowering and anti-hyperten-

sive medication was confirmed by linking the FinnDiane data

to the nationwide Drug Prescription Register maintained by

the Social Insurance Institute of Finland. The register

contains complete information on all prescribed, purchased

and reimbursed medications in outpatient care using the

Anatomical Therapeutic Chemical (ATC) classification codes

for the medications.

Data on alcohol consumption and smoking habits were

collected with questionnaires and were available from 3608

patients. Patients were specifically asked how much beer (one

third of a litre bottles), wine (glasses) and spirits (decilitres)

they were drinking per week. The previous alcohol con-

sumption was also inquired.

The amount of alcohol consumed was then translated to

standard drinks as 33 cl for beer, 12 cl for wine or 4 cl for

spirits each containing 12.0 g pure alcohol. The patients

were divided into five different groups according to their

alcohol consumption in grams per week. Those who had

given up alcohol were grouped separately as former users.

The limit for heavy drinking was based on the Finnish

Current Care Guidelines (www.kaypahoito.fi). Because the

limit of heavy drinking is classified differently for men (≥ 24

doses or 288 g per week) and women (≥ 16 doses or 192 g

per week), the groups were formed differently for men

(lifelong abstainers 0 g/week, light consumers 0–83.9 g/

week, moderate consumers 84–287.9 g/week, heavy con-

sumers ≥ 288 g/week) and women (lifelong abstainers 0 g/

week, light consumers 0–59.9 g/week, moderate consumers

60–191.9 g/week, heavy consumers ≥ 192 g/week).

The analyses based on a particular type of alcoholic

beverage were conducted only among the current alcohol

users. For these analyses, the patients were divided into

different groups according to the type of beverage (wine, beer,

spirit) they were predominantly consuming (> 75%). The

remainder of the patients were classified as mixed drinkers.

The ethics committees of all participating centres approved

the study protocol. Written informed consent was obtained

from each patient and the study was performed in accor-

dance with the Declaration of Helsinki as revised in the year

2000.

Statistical analyses

Data are presented as means � SD for normally distributed

values and as median with interquartile range for non-nor-

mally distributed values and percentages. Differences

between groups were analysed with analysis of variance

(ANOVA) or non-parametric Kruskal–Wallis test when the

data did not meet the requirements for a parametric test; i.e.

What’s new?

• Only a few studies have previously addressed the

association between alcohol consumption and diabetic

microvascular complications with conflicting results.

• Our study shows an association with alcohol consump-

tion and diabetic nephropathy and severe retinopathy.

• The lifelong abstainers and former users of alcohol have

a higher risk of nephropathy and severe retinopathy

compared with light consumers.

• Moderate and heavy consumers carry the same risk of

nephropathy and severe retinopathy as the light con-

sumers.

• The previous studies have not compared different

beverage types. In our study, consumers of alcoholic

spirits have a higher risk of both nephropathy and

severe retinopathy compared with wine drinkers.

ª 2013 The Authors.Diabetic Medicine ª 2013 Diabetes UK 157

Research article DIABETICMedicine

were not normally distributed [age, age at onset of diabetes,

duration of diabetes, triglycerides, apolipoprotein A-I

(ApoA1), C-reactive protein (CRP) and estimated glucose

disposal rate]. Categorical variables were analysed using the

v2-test.The association between alcohol consumption and

nephropathy as well as retinopathy was studied using a

cross-sectional approach. Logistic regression analyses were

performed in a multivariate manner. The analyses were

conducted, adjusting for age at onset of diabetes, sex,

duration of diabetes, triglycerides, HDL cholesterol, HbA1c,

social class, BMI, smoking status, hypertension and

lipid-lowering medication. The criteria for hypertension

were blood pressure 130/80 mmHg or higher or use of

anti-hypertensive medication. The interaction terms between

sex and the amount of alcohol and between sex and the type

of beverage were entered in to the models. In the case of no

interaction, men and women were pooled in the analyses,

otherwise the modelling was performed separately for men

and women.

In a second model, the results were additionally adjusted

for the estimated glucose disposal rate to measure the insulin

sensitivity; HbA1c, BMI and hypertension were not included

in this model as separate covariates. Estimated glucose

disposal rate was calculated with an equation modified for

HbA1c instead of HbA1, [estimated glucose disposal

rate = 24.4 � 12.97 9 waist–hip

ratio � 3.39 9 anti-hypertensive treatment or blood pres-

sure ≥ 140/90 mmHg (yes = 1, no = 0) � 0.60 9 HbA1c].

In addition, the results for the type of beverage were adjusted

for the amount of alcohol consumed.

The light consumers were used as a reference group for the

stratification according to amount of alcohol consumed,

while the wine consumers were used as a reference group for

the comparison between types of beverage. Results are

presented as odds ratios with 95% confidence intervals. All

analyses were performed using Statistical Analysis System

version 9.2 (SAS Institute, Cary, NC, USA).

Results

A total of 721 patients had nephropathy and 1191 had

retinopathy. The median age was 37.4 (28.9–46.8) years and

the median duration of diabetes 21.2 (12.1–30.6) years.

The clinical characteristics of the study population are

shown in Table 1. Proportion of men, duration of diabetes,

systolic blood pressure, total cholesterol, HDL cholesterol,

ApoA1 and prevalence of smoking increased with increasing

amount of alcohol consumed. The proportion of nephrop-

athy, retinopathy and cardiovascular events was the lowest

in the light consumers. Light consumers also had the highest

estimated glucose disposal rate, indicating that they were

more insulin sensitive.

Table 2 shows patient characteristics stratified by each

beverage type. The vast majority of the wine drinkers were

women, while the spirit drinkers were predominantly men.

BMI, HbA1c, triglycerides and daily dose of insulin were the

lowest among the wine drinkers. They also had a more

favourable lipid profile and the highest estimated glucose

disposal rate. The spirit drinkers had the highest proportion

of nephropathy, retinopathy and cardiovascular disease.

Figure 1a shows the adjusted odds ratios for associations

between amount of alcohol consumption and nephropathy.

When using light consumers as the reference category, we

observed an increased risk of nephropathy in abstainers with

an odds ratio of 1.39 (95% CI 1.05–1.84) and in former

users with an odds ratio of 2.44 (95% CI 1.49–3.99). The

moderate consumers had an odds ratio of 0.97 (95% CI

0.73–1.29) and heavy consumers an odds ratio of 0.77

(95% CI 0.41–1.44). When additionally adjusted for esti-

mated glucose disposal rate, the results remained similar,

with an odds ratio of 1.40 (95% CI 1.04–1.87) for abstainers

and an odds ratio of 2.18 (95% CI 1.29–3.69) for former

users.

The analyses regarding the relationship between alcohol

consumption and retinopathy yielded findings similar to those

of nephropathy (Fig. 1b). Compared with light consumers,

there was an increased risk of retinopathy in abstainers with

an odds ratio of 1.42 (95% CI 1.11–1.82) and in former users

with an odds ratio of 1.73 (95% CI 1.07–2.79). No differ-

ence was observed in the risk of retinopathy with increasing

amount of alcohol consumed. Thus, the odds ratio for

moderate consumers was 0.94 (95% CI 0.74–1.21) and for

heavy consumers 0.91 (95% CI 0.53–1.55).

In the multivariate model including estimated glucose

disposal rate, the abstainers still had an increased risk of

retinopathy with an odds ratio of 1.43 (95% CI 1.11–1.84),

although the risk for former users was no longer significant

with an odds ratio of 1.51 (95% CI 0.92–2.49).

The interaction term between amount of alcohol and type

of beverage was neither significant in the model with

nephropathy nor retinopathy as a dependent variable. This

indicates that the amount of alcohol has a similar effect

regardless of the type of beverage.

There was an interaction between sex and beverage type

(P = 0.03) with regard to risk of nephropathy, showing a

different effect of beverage type in men and women. The

association between beverage type and nephropathy in men

is shown in Fig. 2a. When wine consumers were used as the

reference category, a higher risk of nephropathy was

observed in men who drank spirits, with an odds ratio of

2.80 (95% CI 1.15–6.81). There was no difference between

wine drinkers and beer drinkers, with an odds ratio of 0.83

(95% CI 0.37–1.82), or mixed drinkers with an odds ratio of

1.33 (95% CI 0.60–2.92). In the multivariate model includ-

ing the estimated glucose disposal rate, the results were

attenuated and no difference was seen between the wine and

spirit drinkers. In women there was no difference in the risk

of nephropathy between the different beverage types

(Fig. 2b).



DIABETICMedicine Alcohol and diabetic microvascular complications � V. Harjutsalo et al.

Table

1Patientcharacteristics

accordingto

theamountofalcoholconsumed

Variable

Abstainers

Lightconsumers

Moderate

consumers

Heavyconsumers

Form

erusers

All

P-value*

n(m

en%)

858(36.5)

1690(52.7)

799(65.5)

120(80.0)

141(52.5)

3608(52.6)

<0.0001

Diabetic

nephropathy(%

)24.6

17.6

21.0

20.9

45.4

21.2

<0.0001

Severediabetic

retinopathy(%

)37.9

29.6

32.3

35.0

52.2

33.2

<0.0001

Age(years)

37.5

(27.2–4

7.5)

35.6

(27.7–4

5.3)

39.7

(31.8–4

8.0)

42.6

(35.7–4

8.8)

40.2

(33.1–4

8.2)

37.4

(28.9–4

6.8)

<0.0001

Ageatonsetofdiabetes

(years)

13.4

(8.1–2

0.7)

13.9

(9.2–2

2.4)

16.1

(10.9–2

5.3)

21.1

(12.9–2

7.2)

14.0

(9.5–2

2.0)

14.3

(9.4–2

2.9)

<0.0001

Durationofdiabetes

(years)

22.4

(12.8–3

2.1)

19.7

(11.4–2

9.0)

22.6

(11.7–3

1.1)

22.5

(11.7–3

2.9)

24.6

(17.2–3

1.9)

21.2

(12.1–3

0.6)

<0.0001

BMI(kg/m

2)

24.6

�3.7

25.0

�3.4

25.4

�3.4

26.3

�4.0

24.8

�3.7

25.0

�3.5

<0.0001

HbA1cmmol/mol(%

)69�

17(8.5

�1.6)

68�

16(8.4

�1.5)

68�

15(8.4

�1.3)

68�

13(8.4

�1.2)

71�

20(8.7

�1.9)

69�

16(8.4

�1.5)

0.02

Cholesterol(m

mol/l)

4.9

�1.0

4.9

�0.9

5.0

�1.0

5.3

�1.0

4.9

�1.3

4.9

�1.0

<0.0001

HDLcholesterol(m

mol/l)

1.3

�0.4

1.3

�0.4

1.4

�0.4

1.4

�0.4

1.2

�0.4

1.3

�0.4

<0.0001

Trigycerides

(mmol/l)

1.0

(0.7–1

.3)

1.0

(0.7–1

.3)

1.0

(0.7–1

.4)

1.2

(0.9–1

.6)

1.1

(0.8–1

.6)

1.0

(0.7–1

.4)

<0.0001

ApoA1(g/l)

133.0

(120.0–1

46.0)

136.0

(132.0–1

51.0)

141.5

(128.0–1

57.0)

154.0

(135.0–1

66.0)

133.0

(120.0–1

46.0)

137.0

(123.0–1

52.0)

<0.0001

Systolicbloodpressure

(mmHg)

133.8

�20.3

132.9

�17.9

135.5

�17.7

141.6

�17.8

139.2

�22.5

134.2

�18.7

<0.0001

Diastolicbloodpressure

(mmHg)

78.4

�10.4

79.2

�9.5

80.0

�10.0

84.4

�9.9

81.2

�11.0

79.5

�10.0

<0.0001

C-reactiveprotein

(mg/l)

2.1

(1.3–4

.1)

1.9

(1.1–3

.9)

1.9

(1.1–4

.1)

2.2

(1.1–4

.3)

2.3

(1.3–5

.6)

2.0

(1.2–4

.0)

0.02

Anti-hypertensivedrugs(%

)43.1

35.3

42.8

51.7

68.1

40.6

<0.0001

Lipid-loweringdrugs(%

)15.4

10.5

15.4

17.5

24.8

13.5

<0.0001

Cardiovasculardisease

hard

event(%

)13.2

7.0

7.8

10.9

20.0

9.3

<0.0001

Smokers(%

)Current

12.4

23.3

34.6

46.7

23.4

24.0

<0.0001

Ever.

28.5

44.7

63.4

72.5

74.5

47.3

<0.0001

Insulindose

(IU

kg�

1)

0.70(0.54–0

.88)

0.67(0.54–0

.83)

0.66(0.53–0

.81)

0.65(0.55–0

.78)

0.74(0.60–0

.87)

0.68(0.54–0

.84)

0.0006

Estim

atedglucose

disposal

rate

(mgkg�1min

�1)

6.2

(4.5–8

.5)

6.4

(4.5–8

.6)

5.3

(3.9–8

.0)

4.6

(3.2–6

.5)

4.6

(3.2–6

.4)

6.9

(4.3–8

.4)

<0.0001

Values

are

expressed

asmean(�

SD),median(interquartilerange)

orpercentages.

*P-valuerefers

toanalysisofvariance

(ANOVA),Kruskal–Wallis

test

orv2-test.

Abstainers:0g/w

eek,Lightconsumers:0–8

3.9

g/w

eek(m

en),0–5

9.9

g/w

eek(w

omen),Moderate

consumers:84–2

87.9/w

eek(m

en),60–1

91.9

g/w

eek(w

omen),Heavyconsumers:≥288g/w

eek

(men),≥1

92g/w

eek(w

omen)



Table

2Patientcharacteristics

accordingto

thebeveragetype

Variable

Wine

Beer

Spirits

Mixed

Alltogether

P-value

n(m

en%)

322(21.7)

1245(61.4)

175(72.0)

867(63.4)

2609(57.9)

<0.0001

Diabetic

nephropathy(%

)15.1

15.6

39.4

20.7

18.8

<0.0001

Severediabetic

retinopathy(%

)29.6

26.4

52.0

32.8

30.7

<0.0001

Age(years)

41.2

(31.7–4

8.8)

34.0

(26.5–4

2.6)

43.6

(33.7–5

2.0)

40.6

(31.6–4

8.9)

37.2

(29.0–4

6.5)

<0.0001

Ageatonsetofdiabetes

(years)

14.3

(9.6–2

3.5)

13.9

(9.3–2

2.2)

15.9

(10.4–2

6.5)

16.3

(10.6–2

5.0)

14.8

(9.8–2

3.7)

<0.0001

Durationofdiabetes

(years)

23.0

(14.6–3

3.2)

18.3

(10.1–2

6.8)

24.3

(16.0–3

4.4)

22.5

(13.0–3

2.5)

20.5

(11.6–2

9.9)

<0.0001

BMI(kg/m

2)

24.8

�3.2

25.0

�3.3

26.1

�4.1

25.4

�3.5

25.2

�3.4

0.001

HbA1cmmol/mol(%

)66�

14(8.2

�1.3)

69�

16(8.5

�1.5)

68�

14(8.4

�1.3)

67�

15(8.3

�1.3)

68�

15(8.4

�1.4)

0.0004

Cholesterol(m

mol/l)

4.8

�0.8

4.9

�0.9

5.1

�1.1

5.0

�0.9

4.9

�0.9

0.0003

HDLcholesterol(m

mol/l)

1.5

�0.4

1.3

�0.4

1.3

�0.4

1.4

�0.4

1.4

�0.4

<0.0001

Triglycerides

(mmol/l)

0.9

(0.6–1

.2)

1.0

(0.7–1

.4)

1.2

(0.8–1

.8)

1.0

(0.7–1

.4)

1.0

(0.7–1

.4)

0.003

ApoA1(g/l)

143.0

(131.0–1

58.0)

136.0

(123.0–1

51.0)

135.5

(121.0–1

57.0)

139.0

(125.0–1

56.0)

138.0

(124.0–1

54.0)

<0.0001

Systolicbloodpressure

(mmHg)

131.6

�16.9

132.2

�17.2

142.0

�19.2

136.2

�18.5

134.1

�17.9

<0.0001

Diastolicbloodpressure

(mmHg)

78.5

�9.3

79.5

�9.8

81.3

�10.8

80.2

�9.6

79.7

�9.8

0.01

C-reactiveprotein

(mg/l)

1.8

(1.1–3

.6)

1.9

(1.1–4

.0)

2.5

(1.4–5

.4)

1.9

(1.1– 4

.0)

1.9

(1.1–4

.0)

0.0008

Anti-hypertensivedrugs(%

)36.0

32.9

62.9

42.0

38.3

<0.0001

Lipid-loweringdrugs(%

)11.8

8.4

26.9

15.2

12.3

<0.0001

Cardiovasculardisease

hard

event(%

)7.2

4.6

20.6

8.9

7.4

<0.0001

Smokers(%

)Current

14.0

31.9

38.5

25.1

27.8

<0.0001

Ever

36.5

53.2

72.4

51.9

52.0

<0.0001

Insulindose

(IU

kg�1)

0.61(0.49–0

.74)

0.71(0.56–0

.86)

0.63(0.51–0

.79)

0.65(0.54–0

.79)

0.67(0.54–0

.82)

<0.0001

Alcoholconsumption(g/w

eek)

24.0

(12.0–4

8.0)

36.0

(18.0–7

2.0)

75.0

(33.0–1

50.0)

72.0

(42.0–1

32.0)

48.0

(24.0–9

6.0)

<0.0001

Estim

atedglucose

disposal

rate

(mgkg�1min

�1)

6.8

(5.0–9

.0)

6.3

(4.4–8

.5)

4.6

(3.5–6

.3)

5.6

(4.0–8

.1)

6.0

(4.2–8

.4)

<0.0001

Values

are

expressed

asmean(�

SD),median(interquartilerange)

orpercentages.

*P-valuerefers

toanalysisofvariance

(ANOVA),Kruskal–Wallis

test

orv2-test.




The interaction term between sex and beverage type was

not significant for the risk of retinopathy (P = 0.71). The

spirit drinkers, both men and women, also had a higher risk

of retinopathy compared with wine drinkers, with an odds

ratio of 2.32 (95% CI 1.35–4.00) (Fig. 2c). The association

decreased in the multivariate model including estimated

glucose disposal rate and was no longer significant. The

patients who consumed predominantly beer or mixed alcohol

products had a similar risk of retinopathy as the wine

drinkers.

Discussion

This study shows that not only the amount of alcohol, but

also the type of beverage is associated with the risk of

microvascular complications in patients with Type 1 diabe-

tes. The results indicate an increased risk of nephropathy and

retinopathy among lifelong abstainers compared with the

light consumers. Former users of alcohol also had a higher

risk of nephropathy and retinopathy. However, the risk of

nephropathy and retinopathy was not associated with an

increasing amount of alcohol consumed as there was no

difference between light consumers and moderate or heavy

consumers. Spirit drinkers had a higher risk of nephropathy

and retinopathy compared with wine drinkers.

Results are in accordance with the results of the EURO-

DIAB study. In the EURODIAB, there was no significant

difference between moderate and heavy consumers, as also

shown in the present study. In contrast to our results, one

earlier and smaller study concerning the relationship between

alcohol and retinopathy found an increased risk of severe

retinopathy among heavy drinkers [4]. Later, in line with our

results, the Wisconsin Epidemiologic Study observed that the

amount of alcohol consumed does not appear to increase the

risk of proliferative retinopathy, but may even have a

beneficial effect [5].

A J-shaped relationship between alcohol consumption and

disease risk is often shown in previous macrovascular studies

[9]. The absence of this kind of relationship in this study

could be explained by the fact that the former users of

alcohol were grouped separately from abstainers and patients

currently using alcohol, and this group had in fact the highest

(a) (b)

FIGURE 1 The association of the amount of alcohol consumed. Light consumers were used as reference group. (a) Multivariate odds ratios and 95%

confidence interaval for nephropathy. (b) Multivariate odds ratios for retinopathy. *P < 0.05, †P < 0.001.

(a) (b) (c)

FIGURE 2 The association of the beverage type. Wine consumers were used as reference group. (a) Multivariate odds ratios and 95% confidence

intervals for nephropathy in men. (b) Multivariate odds ratios and 95% confidence intervals for nephropathy in women. (c) Multivariate odds ratios

and 95% confidence intervals for retinopathy. *P < 0.05.



risk of both nephropathy and retinopathy. A similar

L-shaped relation, as shown in our study, was reported in

the most recent meta-analysis including studies assessing the

effect of alcohol consumption on cardiovascular disease. The

meta-analyses showed no increased risk of coronary heart

disease with increasing alcohol consumption, although the

risk of total mortality was increased in heavy consumers

[10]. In the present study, the patients that had stopped

drinking alcohol had the highest risk of nephropathy and

retinopathy. Their HbA1c and triglyceride concentrations

were also higher and HDL and ApoA1 lower compared with

the other patients. This at least in part explains the higher

risk of complications seen in this particular group of patients.

The former users also had higher blood pressure compared

with the abstainers or the light-to-moderate consumers, as

well as the highest percentage of cardiovascular disease. Even

the proportion of ‘ever smokers’ was the highest in this

group. Furthermore, they were taking more anti-hypertensive

and lipid-lowering medication and their daily insulin dose

was the highest. Therefore, it is still likely that their medical

condition could have resulted in an altered alcohol

consumption pattern.

Although the mechanism of how alcohol works is still

unresolved, it is widely accepted that moderate alcohol

consumption has beneficial effects on insulin sensitivity and

the lipid profile [11]. In the present study, the estimated

glucose disposal rate decreased gradually with the increasing

amount of alcohol and was the lowest among heavy and

former users, indicating an increase in insulin sensitivity in

light consumers compared with other groups. Poor glycaemic

control is one of the most important risk factors for the

development of both diabetic nephropathy and retinopathy

[12,13]. In the present study, the former users had the highest

HbA1c values combined with a low estimated glucose

disposal rate, indicating that they had poorer glycaemic

control and were more insulin resistant. This could partly

explain their higher risk of nephropathy and retinopathy.

The association was not as clear when comparing the

different types of beverages. Although the beer drinkers

had the highest HbA1c values, their risk of nephropathy and

retinopathy remained the same as for the wine drinkers.

However, when calculated with estimated glucose disposal

rate, the spirit drinkers appeared to be more insulin resistant

compared with others. When the multivariable analyses

included estimated glucose disposal rate, the difference

between wine and spirit drinkers was no longer significant.

It seems that the risk reduction in nephropathy and retinop-

athy seen in light consumers and wine consumers is associ-

ated with better glycaemic control and insulin sensitivity.

With regard to the lipids, the risk reduction is largely

explained by the increase in HDL cholesterol [14]. It has

previously been shown that lipid abnormalities are associated

with increased risk of nephropathy and retinopathy [15,16].

Also in the present study, we observed an increasing trend of

HDL with the increasing amount of alcohol consumed.

When the results were adjusted for HDL in the multivariate

model, the risk of complications was still higher in the

abstainers compared with those patients currently consuming

alcohol. One possible explanation for this observation is that

alcohol affects the development of microvascular complica-

tions through other biochemical mechanisms such as inflam-

mation, adipokines and endothelial function [17–20]. An

increase in inflammatory markers, CRP and interleukin 6

(IL-6) has been shown in patients with nephropathy [21]. In

the present study, the CRP was lower in light consumers and

moderate consumers compared with abstainers, but higher in

heavy consumers and former users.

It is not fully understood whether alcohol per se, rather

than the other components of alcoholic beverages, is asso-

ciated with microvascular complications. Some studies have

shown more beneficial effects of wine and beer on the

endothelial function and risk of cardiovascular disease

[22,23]. However, there is a growing body of evidence that

the beverage type is not associated with the risk of macro-

vascular disease [24]. While the EURODIAB study analysed

the risk of microvascular complications within types of

beverages, our comparison was conducted between the

different types of beverages. In the current study, the patients

consuming mostly spirits had an increased risk of retinop-

athy. Only men who consumed mostly spirits had an

increased risk of nephropathy. However, a clear minority

of women were spirit drinkers (4.5%) and therefore the small

sample size could explain the lack of difference between wine

and spirit drinkers. It is of note that 18% of the former users

were spirit drinkers, while the percentage of spirit drinkers

among the current users was only 7%. This alcohol

consumption profile may explain the increased risk of

nephropathy and retinopathy among the former users.

Blood pressure is one of the major risk factors for

microvascular complications and it is known that alcohol

consumption increases the blood pressure [25,26]. The spirit

consumers had not only the poorest lipid profile, but also the

highest blood pressure. Therefore, the detrimental effect of

spirit consumption is probably mediated through blood

pressure and lipids, as the association was attenuated in the

multivariate model. Obviously it cannot be ruled out that

wine drinkers may also have a healthier lifestyle than spirit

drinkers, as shown in several previous studies [27–29].

Patients consuming different beverage types may also display

differences in their drinking patterns that could have an

effect on the disease outcome [30]. It is of note that the amount

of alcohol consumedwas similar in the spirit drinkers andmixed

drinkers. However, their risk profiles differed significantly. It

could thus be hypothesized that these two groups of patients

might have major differences in their drinking patterns.

The strength of our study is the large sample sizewith precise

data for each participant, including test results of the most

relevant biomarkers.As inmost studies on alcohol, the amount

of alcohol consumedwas based on self-reported weekly doses.

The cross-sectional study design has its limitations and cannot




give a direct answer on cause and effect, because it is not

known if patients have changed their drinking patterns after

the diagnoses of nephropathy or retinopathy or whether

alcohol was involved in the development of complications.

The alcohol questionnaire did not include questions about the

frequency of alcohol consumption, so we could not take the

drinking pattern into account. However, in contrast to many

other studies, we did have valuable information about the

former use of alcohol, which enabled us to exclude the possible

‘sick quitters’ from our group of abstainers.

In conclusion, we show an association between alcohol

consumption and both nephropathy and retinopathy. The

patients drinking mostly spirits had an increased risk of

nephropathy and retinopathy. However, more studies are

needed, as it is not clear if it is the beverage type or the

drinking pattern that causes this association. The risk of

nephropathy and retinopathy did not increase with the

increasing amount of alcohol consumed. On the contrary, we

could see a lower risk of microvascular complications in the

patients who consume alcohol compared with abstainers as

far as they consume mild alcoholic beverages. We emphasize

the fact that the former users of alcohol had the highest risk

of complications. At an individual level, alcohol consump-

tion should be evaluated, taking into account its overall

effect on chronic conditions and possible devastating acute

outcomes, such as intoxication, hypoglycaemia and injuries,

alongside the risk of alcohol dependency. It is still unclear

who will gain from a moderate consumption and therefore

we cannot use the data from this observational study as the

bases for any recommendations of alcohol consumption in

patients with Type 1 diabetes.

Funding sources

This research was supported by grants from the Folkhalsan

Research Foundation, Academy of Finland (134379),

Wilhelm and Else Stockmann Foundation and Liv och Halsa

Foundation. The funding sources were not involved in the

design or conduct of the study.

Competing interests

P-HG has received lecture honorary honorariums from Boeh-

ringer Ingelheim, Genzyme, Novartis, Novo Nordisk, MSD,

Eli Lilly and Medscape and is an advisory board member for

Boehringer Ingelheim, Novartis and Abbott. P-HG has also

received investigator-initiated study grants from Eli Lilly and

Roche. VH, MF and CF have nothing to declare.

Acknowledgements

The authors would like to acknowledge all physicians and

nurses at each FinnDiane centre participating in patient

recruitment and characterization (see Supporting Informa-

tion, Appendix S1).

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Supporting Information

Additional Supporting Information may be found in the

online version of this article:

Appendix S1. The Finnish Diabetic Nephropathy Study

Centres.




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