Diabetes is becoming the leading cause of death in developing countries. Asymptomatic thyroid dysfunction is more common in diabetic population, particularly in type 1diabetes. High frequency of Hashimotos thyroiditis in type 1 diabetes cases has also been reported. The present study evaluates the levels of TSH, TmAb and lipid parameters in 36 type1 diabetes cases. TSH was significantly elevated in cases and TmAb was identified in 7 of the 36 cases studied. Presence of TmAb and elevation in TSH were more pronounced in female cases. Serum total cholesterol as well as LDL- cholesterol levels were significantly elevated and Serum HDL-cholesterol was significantly lowered in type 1 diabetics. Elevation in serum total cholesterol was more conspicuous in cases with thyroid antibodies.

Muralidhara Krishna C S*, C Vibha*, Manohar C S***,   G S Anil Kumar*,

K Nanda* ,G  Sadanand*, Nisarga**, K L Mahadevappa*

 

*Department of Biochemistry, **Paediatrics and ***Surgery, KempeGowda Institute of Medical Sciences and Samatvam Endocrinology Diabetes Centre, Bangalore, Karnataka.

Address for Correspondance:

Dr. C S Muralidhara  Krishna

Department of Biochemistry

Bangalore Medical College & Research Institute

Fort, K.R. Road, Bangalore 560 002

Karnataka

Ph: 080- 26700810

Email: muralidharakrishna@yahoo.com

 

KEY WORDS

Type1 diabetes; TSH (Thyroid stimulating hormone); TmAb (Thyroid microsomal antibodies)

INTRODUCTION

Diabetes mellitus and thyroid diseases are two common endocrinopathies seen in general population. Insulin and thyroid hormones are intimately involved in cellular metabolism and thus an excess or deficit of either of these hormones could result in the functional derangement of the other. The present investigation is an attempt to study how diabetes affects thyroid function in euthyroid individuals and conversely how thyroid diseases could affect glycemic control. It is also of interest to assess how both the diseases superimposed could affect the lipid parameters and thereby the general well being of the individuals.

Thyroid function is affected in diabetes (1).  Hypothyroidism among diabetics has been   frequently encountered (2). Incidence of goiter in diabetics under the age of 40 years was higher compared to the diabetics over 40 years (3). Asymptomatic thyroid dysfunction is one of the more common occurrence in diabetic population particularly in type 1 diabetes (IDDM) (4). The prevalence of hypothyroidism in Type 1 diabetes  is higher in females than in males (5). Hypothyroidism is found in about 3% of patients with type 1 diabetes. Moreover, 13 to 20% of Type 1 diabetic patients have elevated blood TSH levels and anti-thyroid antibodies. Thyroid microsomal (peroxidase) antibodies are present in 5 to 40% of type 1 diabetes patients, and significant number of these patients present with or develop thyroid dysfunction (6). Miguel Fernandez-Castaner et al  reported that nearly one-third of newly diagnosed type 1 diabetes patients have coexistent thyroid autoimmunity with a high prevalence of thyroid dysfunction (7). The frequency of autoimmune thyroiditis in type 1 diabetic adults is higher in young adults than in children (4). Adolescent girls and young women are especially affected (8).Type 1 diabetes mellitus in children and adolescents often present with autoimmune thyroid disorders (9). Indeed type 1 diabetes may appear at any younger age, the onset may be insidious and even asymptomatic for a long time.        Individuals with insulin dependent diabetes mellitus frequently develop Hashimoto’s thyroiditis defined by high titres of thyroid peroxidase (TPO/TmAb) or thyroglobulin antibodies, elevated TSH in the absence of medications, and/or a positive history on examination (10). Although many persons with Hashimoto’s thyroiditis are hypothyroid, there is a sub-group of euthyroid cases with high titres of thyroid autoantibodies and normal thyroid function who do not require medication. However, some of these individuals may become hypothyroid as they age. Should this occur among persons with Type 1 diabetics, the decrease in basal metabolic rate due to untreated hypothyroidism may cause serious illness and further complicate lipid disturbances, metabolic control and risk of adverse pregnancy outcome (11-12).

The lipid profile of patients with type 1 diabetes mellitus is highly dependent on glycemic control.  Individuals with poorly controlled type 1 diabetes mellitus show high levels of total triglyceride, total cholesterol and variable concentration of high-density lipoprotein cholesterol (HDL-C) compared with non-diabetic control subjects (13-14). Diabetes mellitus has been found to be an important risk factor for macrovascular disease in adults (15). Both type 1 and type 2 diabetes mellitus are associated with increased risk of CHD. Cardiac mortality was the leading cause of death in type 1 and type 2 diabetes (16). In United States, coronary disease is responsible for 25% of deaths between ages of 30-55 years in type 1 diabetes compared with only 6% in the general population (17). In type 1 diabetes patients the risk for silent myocardial ischaemia is more prevalent at the stage of incipient diabetes nephropathy (18).Coronary heart disease (CHD) occurs earlier and more frequently in diabetics and is a leading cause of death in type 1 diabetes (17). Abnormalities in lipid and lipoprotein levels have been reported in type 1 diabetes mellitus and are indicated to be the cause of CHD (15). Altered lipid and lipoprotein profile has also been recorded in hypothyroidism (19). The relationship between subclinical hypothyroidism and an atherogenic lipid profile is still not very clear. Dyslipidaemia in type 1 diabetes mellitus, particularly with hypothyroidism superimposed, thus becomes an highly interesting aspect for a detailed study.

The present study involves the estimation of TSH and TmAb levels in type 1 diabetes mellitus and correlating them with lipid parameters to assess the thyroid dysfunction, autoimmunity and other consequences.

 

 

MATERIAL AND METHODS

The present study is carried out on known type 1 diabetes mellitus (IDDM) patients attending the clinical departments of Kempegowda Institute of Medical Sciences and Research Centre and Samatvam Endocrinology Diabetes Centre, Bangalore. Study was conducted on well-managed 36 type 1 diabetes mellitus patients  and 30 healthy controls aged between 5 to 30 years. Among these 36 type 1 diabetes mellitus patients, 26 were females and 10 were males. Among 30 controls 21 were females and  9 were males. Patients with complications of type 1 diabetes mellitus or any other complications were excluded from the study.

12 hour overnight fasting venous blood samples were collected from these subjects and the samples were processed for the estimation of fasting blood glucose, serum total cholesterol, serum triglycerides, HDL-cholesterol, serum TSH, TmAb, serum creatinine and serum albumin. LDL -cholesterol and VLDL -cholesterol values were calculated from the values of total cholesterol, triglycerides and HDL -cholesterol by applying Friedwald equation (Patients with triglycerides levels  > 400 mg% was excluded). Fasting urine sugar, ketone bodies and albumin levels were assessed by Dipstick method.  Estimation of Thyroid Stimulating Hormone (TSH) was by ELISA.(20) and detection and titration of  TmAb by Indirect Agglutination Method. The TmAb measurements were made using the procedure and reagents supplied by FUJI REBIO INC., Japan (SERODIA-AMC, India).

 

STATISTICAL METHODS

Student t test of independent samples has been used to find the significance of difference between the cases and controls for various parameters and between the group A and Group B in cases. The significance level of 5% is taken as critical value to see the difference between the mean values of cases and controls (21).

 

Statistical software: The Statistical software namely SPPS 10.0 and Systat 8.0 were used for the analysis of the data and Microsoft Word and Excel have been used to generate graphs, tables etc.

RESULTS

Table 1 Presents the  sex and age distribution of controls and cases. Levels of FBS, TSH and TmAb along with the serum lipid parameters is presented in Table 2. In the cases studied elevation in FBS and TSH was highly significant . TmAb, serum total cholesterol and LDL cholesterol were also elevated significantly with serum HDL cholesterol recording significantly lower level. Table – 3 presents the level of TSH , TmAb and lipid parameters in type 1 diabetic cases with and without antibodies. The difference was highly significant in the case of TSH and TmAb, whereas in the case of total cholesterol and LDL cholesterol it was moderately significant. The data on lipid parameters in the two groups is also projected in Fig. -1. Scatter plot of FBS vs TSH, FBS vs Total cholesterol, FBS vs HDL cholesterol and FBS vs LDL cholesterol is in Fig-2,3,4 and 5 respectively. The scatter plot generally suggest a fairly positive correlation of FBS with the parameters compared in the plots.

The values of serum creatinine, albumin as well as fasting urine sugar, ketone bodies and protein (albumin) were all in the normal range.

Table- 1.  Age and Sex Distribution in the Controls and Cases

Groups

Sex

Mean age in years   (5 to 30 years)

Controls (n=30)

Male

9

23.93 ± 6.41

Female

21

Cases (n=36)

Male

10

22.19 ± 8.18

Female

26

Table – 2  FBS, TSH, TmAb titre values and lipid parameters in Controls and Cases

Biochemical Parameters

Controls (n=30)

Cases (n=36)

P value

FBS (mg/dl)

80.90 ± 8.33

152.64 ±  51.78

< 0.0001

TSH (mIU/ml)

1.46 ± 0.66

2.69 ± 2.39

< 0.008

TmAb (Titre value)

1:102 ± 0.0

1: 162.52

< 0.05

Total Cholesterol (mg/dl)

165.30 ± 43.76

187.67 ± 46.51

< 0.05

Triglycerides (mg/dl)

103.23 ± 37.59

128.06 ± 89.24

< 0.16

HDL  cholesterol (mg/dl)

45.23 ± 5.30

42.14 ± 7.15

< 0.05

LDL  cholesterol (mg/dl)

99.43 ± 37.54

119.83 ± 37.73

< 0.03

VLDL  cholesterol (mg/dl)

20.63 ± 7.55

25.58 ± 17.78

< 0.16

 

 

 

 

 

Table – 3. TSH, TmAb and Lipid Profile in type 1 diabetic cases with thyroid antibodies

(Group A) and without thyroid antibodies (Group B)

 

Biochemical
Parameters

Group

A=7 cases, B=29 cases

Mean ± SD

P

TSH

A

7.13    ±     1.64

<0.0001

B

1.61 ± 0.66

TmAb

A

1:367.852 ± 1:352.542

<0.0001

B

1:102 ±  0.00

TC

A

227.29 ±   63.02

<0.010

B

178.10 ±   36.96

TG

A

142.43  ±   75.96

<0.642

B

124.59 ± 93.02

HDL-C

A

44.86 ±   9.89

<0.269

B

41.48 ±  6.39

LDL-C

A

154.00 ±  48.03

<0.006

B

111.58 ±  30.38

VLDL-C

A

28.43 ± 15.06

<0.644

B

24.89 ± 18.55

 

TC- Total cholesterol, TG- Triglycerides, HDL-C – High density lipoprotein cholesterol, LDL-C- Low density lipoprotein cholesterol, VLDL- C- Very low density lipoprotein cholesterol

Fig 1: Serum lipid profile in type 1 diabetic cases with and without thyroid antibodies

serum lipid profile

Fig. 2a Scatter plot of FBS Vs. TSH among Controls

scatter plot of fb

Fig 2b Scatter plot of FBS Vs. TSH among Cases

ijbms

Fig 3a Scatter plot of Total Cholesterol Vs. FBS among Controls

ijbms

Fig 3b Scatter plot of Total Cholesterol Vs. FBS in Cases

ijbms

Fig 4a Scatter plot of HDL Cholesterol Vs. FBS in Controls

ijbms

 

 

Fig 4b Scatter plot of HDL Cholesterol Vs. FBS in Cases

ijbms

Fig 5a Scatter plot of LDL Cholesterol Vs. FBS in Controls

ijbms

Fig 5b Scatter plot of LDL Cholesterol Vs. FBS in Cases

ijbms

DISCUSSION

Data on FBS levels in controls and cases indicates a poor glycemic control in cases. Glycemic state strongly influences the serum T3 levels and TSH levels and poorly controlled diabetes results in a low T3 state (22). In hypothyroidism that is encountered in type 1 diabetes, the synthesis and release of insulin is decreased accounting for impaired glycemic control as well as recurrent hypoglycaemia due to decreased hepatic output (23). In addition to the impact of altered thyroid status per se on diabetes, hypothyroidism with a decrease in the secretions of growth hormone and glucocorticoids further affects glucose homeostasis (24-25).

TSH levels are significantly elevated in cases compared to the controls. TSH values in cases and controls in the present study is clearly suggestive of the hypothyroid state that is commonly associated with type 1 diabetes mellitus. There are a number of reports on the TSH levels in type 1 diabetes mellitus and many of them have recorded elevated TSH levels (4-5; 26-27). TSH levels are recorded to be higher in female type 1 diabetic cases (5). Lowered TSH level has been reported in type 2 diabetes mellitus (1). In euthyroid individuals with diabetes mellitus the serum T3 levels, basal TSH levels and TSH response to TRH may all be strongly influenced by the glycemic control. Poorly controlled diabetes may also result in impaired TSH response to TRH or loss of normal nocturnal TSH peak. TSH responses and low T3 state may normalize with good glycemic and/or diabetes control. The normal nocturnal TSH peak may not be restored in C-peptide negative patients i.e. patients with totally absent pancreatic b cell function (22).

The association between type 1 diabetes and autoimmune thyroid disease has long been recognized and a high prevalence of thyroid antibodies has been found (8 to 44%) in several studies (28-30) is an indicator of thyroid autoimmune disease or Hashimoto’s disease. The prevalence of TmAb is higher in females than in males (5) and in adults than in children (8). In the present study thyroid microsomal antibody (TmAb or TPO) titre values in serum is significantly elevated in cases when compared to the controls. In seven out of thirty six cases (7/36) TmAb titre values are appreciably elevated. Thyroid function was apparently normal in the cases studied. Nearly one-fifth of the type 1 diabetic cases have co-existent thyroid antibodies (TmAb). As is reported in the literature (31), elevation in TmAb titres is encountered only in type 1 diabetic cases with increased TSH values. About 1/4th of Thai patients with type 1 diabetes without thyroid disease had thyroid antibodies (32). A strong association between autoimmune thyroid antibodies (TmAb) and type1 diabetes has been indicated by Umpierrez et al (33).

The present investigations on serum lipid profile in type 1 diabetic cases compared to the controls report a significant elevation in total cholesterol and LDL- cholesterol. The serum levels of triglycerides and VLDL-cholesterol though elevated are not statistically significant. The values of HDL- cholesterol are significantly lowered. Among persons with type 1 diabetes mellitus, the decrease in basal metabolic rate (BMR) due to untreated hypothyroidism that commonly occurs may cause serious illness and further complicate lipid disturbances (31), but unlike in NIDDM, the prevalence of dyslipidaemia in IDDM is not large. Gray et al (34) have reported elevated total cholesterol and triglyceride in diabetics with increased level of TSH and dyslipidaemia is dependent on glycemic control. In the cases of subclinical hypothyroidism (increased TSH), elevated total cholesterol, triglycerides and LDL-C with comparable HDL-C have been reported by Nadia Caraccio et al (19). Antonio Perez et al (35) have cited several papers in which individuals with poorly controlled type 1 diabetes mellitus show high levels of total cholesterol and triglycerides with variable concentrations of HDL cholesterol. They have also reported elevated LDL-C and triglyceride levels with low HDL-C levels in IDDM cases. Dyslipidaemia is indicated to normalize to some degree with good glycemic control and lipidemic changes appear to be more evident in females than males. Indeed more frequent dyslipidaemic disorders in IDDM cases is low HDL-C, low prevalence of hypertriglyceridaemia and higher incidence of elevated total cholesterol. Given the link of increased LDL-C and lowered HDL-C levels with CAD in diabetics in general and in type 1 diabetic cases with thyroiditis (hypothyroidism) in particular, the results of this and other similar studies strongly project the need for evaluation of lipid profile as well as thyroid status in type 1 diabetic cases. Indeed several studies have suggested a need for regular screening of type 1 diabetics for TSH levels and lipid profile.

CONCLUSION

  • Serum TSH and TmAb levels are elevated in the experimental group (IDDM cases) when compared to the controls. Among the IDDM cases studied, the changes in TSH and TmAb is highly conspicuous in 7 out of 36 cases.
  • Increase in serum TSH and TmAb values are more pronounced in IDDM females.
  • Significant elevation in serum total cholesterol and LDL-cholesterol levels is observed in IDDM cases. Raise in the serum Triglycerides and VLDL-cholesterol levels are not statistically significant. Serum HDL–cholesterol levels are significantly lowered.
  • From among the IDDM cases, elevation in serum total cholesterol and LDL-cholesterol levels is highly significant in the cases with thyroid antibodies (7 cases) compared to the cases without antibodies (29 cases). Serum HDL-Cholesterol level is comparable in the two sub groups of IDDM cases studied.

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