Diabetes Mellitus is heterogenous group of metabolic disorders characterized by chronic hyperglycaemia with disturbance of carbohydrate, fat and protein metabolism. It results from defects in  insulin secretion, insulin action or both. The effect of diabetes mellitus includes long term damage, dysfunction and failure of various organs, eyes, kidneys, nerves and heart and blood vessels. Several distinct types of DM are caused by complex interaction of genetics and environmental factors.^[1] Type 2 diabetes mellitus is metabolic and endocrinological disease characterized by hyperglycaemia associated with insulin resistance and/or defective insulin secretion.^[2] The persistence of these metabolic                  disturbances leads to permanent and irreversible functional and structural changes in the cells of the body which in turn lead to the development of "diabetic complications", characteristically affecting, the    cardiovascular system, eye, kidney and nervous system mainly.^[3] Risks of incidence from CAD or fatal CAD are two- to four fold higher in people with DM than in those  without. Furthermore, long-term prognosis after a coronary event is significantly worse among people with DM than those without.^[4] Accordingly, the National Cholesterol Education Program (NCEP) guidelines classify DM as a CAD "risk equivalent" a disorder that carries an absolute, 10-year risk for developing new major coronary events equal to that of non-diabetic persons with established CAD (i.e., less than 20%). However, the core metabolic defect in DM (i.e. hyperglycemia) does not by itself raise the risk to the level of a CAD risk equivalent - it is a constellation of metabolic risk factors that combine with hyperglycemia to impart a high risk.^[5] Diastolic heart failure (HF) is also referred to as HF, with preserved left ventricular systolic function. Many studies have reported that the incidence of heart failure in diabetic subjects is high even in the absence of hypertension and coronary artery disease. Studies have reported a high prevalence of pre- clinical diastolic dysfunction among subjects with DM. The evidence indicates that myocardial damage    in diabetic subjects affect diastolic function before the systolic function.^[6] Diabetic cardiomyopathy has been proposed as an independent cardiovascular disease, and many mechanisms, such as microvascular disease, autonomic dysfunction, metabolic disorders, and interstitial fibrosis, have been suggested as causative factors.^[7]

AIM OF THE STUDY

To assess the diastolic dysfunction in type 2 diabetic patients using Doppler echocardiography.

This was a hospital based cross-sectional study conducted among 100 patients with Type 2 Diabetes Mellitus (DM) who exhibited diastolic dysfunction, admitted to the Department of Medicine, Tertiary Care Hospital, over a period of 2 years after obtaining clearance from institutional ethics committee and written informed consent from the study participants.

Criteria

All patients with diastolic dysfunction diagnosed with Type 2 DM.

Exclusion Criteria

Pregnant women, hypertensive patients, patients with known coronary artery disease, patients with known valvular heart disease or arrhythmias, and those with other comorbidities such as COPD, pre-existing renal disease, and thyroid disorders were excluded from the study.

Statistical Methods

The data were entered and coded into Microsoft Excel for analysis. Categorical data were expressed as rates, ratios, and proportions, while continuous data were expressed as mean ± standard deviation. The Chi-square test and Fisher's exact test were used for the comparison of categorical data, while the independent sample t-test was used for continuous data. A p-value of ≤ 0.05 at a 95% confidence interval was considered statistically significant.

The association between DD Grade and Age Group. The chi square test was applied  to determine the association between two variables, which was found to be statistically significant. (P<0.05)

For the absence group 33.3% was for both age groups 31-40 years and 41-50 years, along  with 16.7% for age groups 51-60 years and >60 years. For the GI grade, 40% was for both age groups 51-60 years and 20% for age groups 31- 40 years, 41- 50 years, and >60 years respectively. For the GII grade, the highest proportion 50% was for age group 51-60 years, followed by 35.7% for age groups 41-50 years. The lower proportion, 10.7% and 3.6% were for age groups 31-40 years and >60 years respectively. For the GIII grade, the highest proportion 50% was for age group >60 years followed by 25% for age groups 51-60 years. The lower proportion, 12.5% were for both age groups 41-50 years and 31-40 years respectively. For the GIV grade, the highest proportion 44.3% was for age group 51-60 years, followed by 33.3% for age groups >60 years. The lower proportion, 11.1% were for both age groups 41-50 years and 31- 40 years respectively.

The association between DD Grade and Sex Group. The chi square test was applied to determine the association between two variables, which was found   to  be statistically significant. (P<0.05)

For the absence group 33.3% was for females and 66.7% was for Males. For the GI grade, 20% was for females and 80% was males respectively. For the GII grade, the lower proportion 35.7% was for females and 64.3% was for males respectively. Similarly, for GIII grade, the lower proportion 25% was for females and 75% was for males respectively. Whereas, for the GIV grade, the highest proportion 77.8% was for females and the lower proportion, 22.2% was for males.

The data presented shows the distribution of Diastolic Dysfunction severity (DD Grade) across rural and urban regions, with corresponding counts and percentages. Diastolic Dysfunction is categorized into five stages: Absent, Grade I (GI), Grade II (GII), Grade III (GIII), and Grade IV (GIV).

The Chi-Square value (10.433) with 4 degrees of freedom and a P-value of 0.034 indicates a statistically significant relationship between region and Diastolic Dysfunction grade. For Absent (No Diastolic Dysfunction) the urban group has a significantly higher percentage (66.7%) of individuals without Diastolic Dysfunction compared to the rural group (33.3%).

For GI (Grade I Diastolic Dysfunction) the distribution of individuals in Grade I is fairly balanced   between rural and urban areas, with a slight edge toward urban areas (52.0%).

In case of GII (Grade II Diastolic Dysfunction) a much higher percentage of urban individuals (67.9%) are in Grade II compared to rural individuals (32.1%). In case of GIII (Grade III Diastolic Dysfunction) a significantly higher percentage of rural individuals (75.0%) are in the advanced stage of Grade III, compared to urban individuals (25.0%).

The data examines the relationship between triglyceride levels and diastolic dysfunction (DD) grades       among 100 individuals. The Pearson Chi-Square test yields a value of 18.326 with a degree of freedom (df) of 12 and a p- value of 0.006, indicating that the relationship between triglyceride levels and diastolic dysfunction             grade is statistically significant (p > 0.05).

For individuals with no diastolic dysfunction, 20.0% have triglyceride levels below 150 mg/dL, 36.7% fall within the 150-199 mg/dL range, 26.7% are in the 200-249 mg/dL range, and 16.7% have levels of 250 mg/dL or higher. In those with Grade I diastolic dysfunction, the majority (56.0%) have triglyceride levels in the 150-199 mg/dL range, followed by 36.0% in the 200-249 mg/dL range, and a      small proportion (8.0%) with levels of 250 mg/dL or higher. No individuals with triglyceride levels below 150 mg/dL are found in this category.

For Grade II diastolic dysfunction, 57.1% of individuals have triglyceride levels in the 150-199 mg/dL  range, followed by 28.6% in the 200-249 mg/dL range, 7.1% with levels below 150 mg/dL, and another 7.1% with levels of 250 mg/dL or higher. In Grade III, 50.0% of cases fall within the 150-199 mg/dL range, 37.5% have levels of 250 mg/dL or higher, and 12.5% fall within the 200-249 mg/dL range. No individuals with triglyceride levels below 150 mg/dL are observed in this grade. Lastly, for the most severe grade (GIV), 66.7% of individuals have triglyceride levels in the 150-199 mg/dL range, followed by 22.2% with levels of 250 mg/dL or higher, and 11.1% in the 200-249 mg/dL range.

Overall, the majority of individuals with diastolic dysfunction, regardless of grade, have triglyceride levels in the 150-199 mg/dL range.

The distribution of the Urine Albumin-to-Creatinine Ratio (Urine Alb Ratio) across different grades of Diastolic Dysfunction (DD Grade). The ratio is divided into three categories: <30 mg/g (normal), 30-300 mg/g (microalbuminuria), and >300 mg/g (macroalbuminuria).

The P-value (0.000) indicates that there is a statistically significant association between the urine albumin-to-creatinine ratio and the DD grade. In other words, the severity of Diastolic Dysfunction (as measured by DD grade) seems to be strongly related to the kidney function measured by the urine albumin ratio in this dataset.

In case of absent the majority (100 %) have a urine albumin ratio of less than 30, indicating normal kidney function. However, 0% exhibit microalbuminuria (30-300), 0% macroalbuminuria (>300), Grade I (GI) Diastolic Dysfunction in individuals with Grade I Diastolic Dysfunction, 100.0%  maintain normal kidney function with a urine albumin ratio of less than 30.

Grade II (GII) Diastolic Dysfunction: For those in Grade II, 100% have a normal urine albumin ratio, showing that a large proportion still have functioning kidneys despite worsening Diastolic Dysfunction.

Grade III (GIII) Diastolic Dysfunction: In Grade III, 50% individuals maintain normal kidney function, which is lower than in earlier grades. A higher proportion 37.5 0%) present with microalbuminuria, and 12.5% show macroalbuminuria, reflecting a notable increase in kidney damage.

Grade IV (GIV) Diastolic Dysfunction: Among individuals with the most severe Diastolic Dysfunction (Grade IV), 33.33% still have a urine albumin ratio of less than 30, suggesting that some individuals maintain normal kidney function despite advanced retinopathy. However, 44.4.3% have microalbuminuria, indicating that a third of this group shows signs of early kidney damage. Also 22.224% in this study group has macroalbuminuria (>300), which might imply that kidney damage is  present and it has reached the most severe stages in these cases. The data presents the relationship between HbA1c levels and the severity of Diastolic  dysfunction (DR).

The Pearson Chi-Square test result (value = 41.303, df = 12, p = 0.000) indicates a statistically significant association between HbA1c levels and the severity of Diastolic dysfunction, suggesting  that as HbA1c levels increase, the severity of Diastolic dysfunction tends to increase.

In the “Absent” the majority of individuals without Diastolic dysfunction have HbA1c levels between 8-10 (53.3%) and 7-8 (46.7%). There are no cases of absent in the higher HbA1c ranges (6-7) and (>10).

In the “Grade I (GI)” mild is most prevalent among those with HbA1c levels between 8- 10 (68%). There are also cases with HbA1c levels between 6-7 (16%) and 7-8 (12%) and >10 (4.0%), suggesting that mild is less common at higher HbA1c levels.

The “Grade II (GII)” shows moderate being most common among those with HbA1c levels between 8-10 (64.3%). There are a few cases 3.6% in the lower range 6-7, and moderate cases in 7-8 (14.3%) and >10.0 (17.9%).

In the “Grade III (GIII)” severe is mainly found in individuals with HbA1c levels between 8-10 (50%) and >10 (37.5%). There are also few cases in the 7-8 (12.5%), but no cases 0% in 6-7 range, indicating  a trend toward increased severity with higher HbA1c levels.

In the “Grade IV (GIV)” very severe is also most frequent among those with HbA1c levels >10 (55.6%) and between 8-10 (33.3%), with fewer cases in the 7-8 (11.1%), and No cases 0% of GIV are observed with HbA1c levels 6-7.

The association between DD Grade and Diastolic Dysfunction Durations Group. The chi square test was applied to determine the association between two variables, which was found to be statistically significant. (P=0.049)

For the absence group 53.3% of cases were for 11-15years, 33.3% for 6-10 years duration, along with 13.3% for duration 0-5 years. For the GI grade, a very low 8.0% cases were for >15 years along with 0.0% for duration 0-5 years, whereas 52% for 6-10 years duration and 40% for duration 11-15 years. For the GII grade, a very low a low 17.9% cases were for >15 years along with 3.6% for duration 0-5 years, whereas 42.9% for 6 -10 years duration and 35.7% for 11-15 years. For the GIII grade, the highest 75% for duration of 6-10 years and 12.5% each for duration of 11-15 years and duration of >15 years. For the GIV grade, the highest proportion 66.7% each was for duration of 6-10 years and 22.2% for duration of >15 years and lower 11.1% for duration of 6-10years.

The data examines the relationship between BMI grades and diastolic dysfunction grades in a sample of 100 individuals. The Pearson Chi-Square test indicates a statistically significant relationship between BMI grade and diastolic dysfunction severity grades (p = 0.000). It reveals that the absence of diastolic dysfunction is most common among those with a normal BMI (90%), few cases who are overweight (10%), with 0.0% for underweight and obese categories.

For Grade I diastolic dysfunction, the majority of cases (48.0%) are found overweight and 36% cases  with a normal BMI, while a smaller portion 7.1% is observed in the obese and underweight groups. In Grade II diastolic dysfunction is also more prevalent in the normal 39.3% and             overweight BMI group (46.4%), with fewer 7.1% cases in the obese group. Same in Grade III diastolic dysfunction is also more prevalent in the normal and overweight BMI group (37.5%), with fewer 25% cases in the obese group.

As the severity of diastolic dysfunction increases, the normal BMI category shows only 11.1% with               the highest prevalence 77.8% for overweight and 11.1% for obese group.

The relationship between the DM Neuropathy symptoms (Absent, Sensory, or Autonomic symptoms) across different grades of Diastolic Dysfunction Grade (Absent, GI, GII, GIII, GIV).

Statistically, the Pearson Chi-Square test yields a value of 64.338 with 8 degrees of freedom and a P value of 0.000, indicating a statistically significant association between DM Neuropathy and DD Grade.

In the Absent Neuropathy category, 91 % of the patients show no signs of neuropathy. This proportion remains high (100%) for patients with no retinopathy (DD Grade: Absent) but decreases         as the severity of neuropathy increases. For example, in DD Grade GI, 96% of patients are free of  neuropathy, which drops further to 96.42% in GII, 50% in GIII, and 55.55% in GIV.

For those with sensory symptoms, 5% of the total population presents with such symptoms. Notably, none of the patients in the DD Grade Absent group exhibit sensory neuropathy, For instance, 4% of patients with GI have sensory symptoms, which increases to 0% in GII and remains  high at 25% in GIII. However, this drops again in GIV to 22.22% suggesting a significant relationship between sensory neuropathy and diastolic dysfunction.

In terms of Autonomic Symptoms, only 4% of the total patients experience this type of neuropathy. These symptoms are absent in the lower grades of DD (Absent, GI, GII) but become more prevalent in the higher grades, with 25% of GIII patients and 11.11% of GIV patients experiencing autonomic                symptoms. This suggests that autonomic neuropathy becomes more common in more advanced stages of retinopathy.

In our study, we observed that the prevalence of diastolic dysfunction (DD) was 63%, with the majority of cases classified as grade I (25%). This prevalence closely aligns with the findings of Faden et al. (2008),^[8] who reported a prevalence of 64% in their study. This consistency confirms  that diastolic dysfunction is a common complication in diabetic patients.

When examining the correlation between HbA1c levels and diastolic dysfunction, our study found that 50% of patients with HbA1c levels greater than 9.5% had grade III or IV diastolic dysfunction. This result is somewhat lower than the findings of Gupta et al. (2015),^[9] who reported that 75.34%       of patients with HbA1c levels greater than 7.5% developed diastolic dysfunction. Regarding the impact of BMI on diastolic dysfunction, our study revealed that 75% of patients with            grade III diastolic dysfunction had a normal BMI, while 22.2% of those with grade IV were overweight. This finding contrasts with the work of Maiello et al. (2016),^[10] who found a higher prevalence of LVDD in obese women with a BMI greater than 30.

In terms of age, our study identified that the highest prevalence of grade II diastolic dysfunction was  in the 51-60 years age group (50%), and the 61-70 years age group had the highest prevalence of grade III diastolic dysfunction (50%). This aligns with Kossaify et al. (2013),^[11] who identified age as a significant predictor of diastolic dysfunction. Gender differences in diastolic dysfunction were also observed in our study, with 77.8% of grade IV cases being female, while 75% of grade III cases were male. This observation is consistent with the general literature, which suggests that post-menopausal women are at a higher risk for diastolic dysfunction due to hormonal changes. Our study provides further evidence of the significant gender  differences in the severity of diastolic dysfunction, particularly in more advanced grades.

Finally, while our study observed that 66.7% of patients with grade IV diastolic dysfunction had               triglyceride levels between 150-199 mg/dL, this association was statistically significant. This contrasts with some studies, like those by Gupta et al. (2015),^[9] and Patil et al. (2011),^[12] which              have suggested a link between dyslipidaemia and cardiac dysfunction.

For the PPBS levels, while our study found statistically significant association between postprandial blood sugar (PPBS) levels and diastolic dysfunction (p = 0.004), that the distribution of diastolic dysfunction grades is not random with respect to the postprandial blood glucose ranges. The higher glucose levels (especially in the range of 350-400 mg/dL) are associated with more severe grades of diastolic dysfunction (GIII and GIV), while lower glucose levels (200-250 mg/dL) are associated with absent or milder grades (Absent or GI).

For the HbA1c levels, both our study and Dr. K. Rohinath's et al^[13] study found a statistically significant association between higher HbA1c levels and the severity of diastolic dysfunction (p < and p = 0.003, respectively). In our study, 93.1% of patients with HbA1c levels >6.4% had diastolic dysfunction, highlighting poor glycemic control as a key factor in the development and progression of cardiac dysfunction.

Glycemic Control (HbA1c)

Melissa Leung’s^[14] study saw significant improvement in HbA1c levels, dropping from 9.6% at baseline to 7.8% at follow-up (P<0.001), with 86.4% of patients achieving better glycemic control. In contrast, our study revealed a higher proportion of patients (58%) in the unsatisfactory glycemic control range (HbA1c 8.0–10.0), with only 5% achieving excellent control (HbA1c 6.0–7.0).

Melissa Leung’s^[14] study reported no significant changes in creatinine levels (P=0.470) or eGFR (P=0.540). In our study, 90% of patients showed no signs of nephropathy, 7% had microalbuminuria, and 3% had macroalbuminuria. This suggests a relatively low prevalence of advanced kidney disease in our cohort, aligning with Melissa Leung’s^[14] findings, where nephropathy complications were also  minimal.

In Madhumathi’s^[15] study, a smaller percentage of patients were on oral hypoglycemic agents (OHAs) alone (64%) compared to our study, where 85% of patients were treated with OHAs. This indicates that OHAs were more commonly prescribed in our study population. Madhumathi’s et al^[15] study also reported that 22% of patients were on insulin alone and 14% were on both OHAs and  insulin. In contrast, only 3% of our study patients were on insulin alone, with 12% on both OHAs and insulin. This suggests a notable difference in treatment patterns, where insulin use in our study was significantly lower.

The higher proportion of OHA use in our study may indicate a patient population with better glycemic control or earlier stages of diabetes, where OHAs are effective, while the lower insulin use suggests fewer patients with advanced or poorly controlled diabetes requiring insulin therapy. This    difference in treatment modalities could also reflect variations in the standard of care, patient adherence, or healthcare accessibility between the two populations.

In Madhumathi’s^[15] study, 44% of patients on OHAs had diastolic dysfunction, whereas in our study, no specific association between diastolic dysfunction and treatment type was mentioned. However, Madhumathi's study shows a relatively balanced distribution of diastolic dysfunction between treatment groups: 14 out of 32 patients on OHAs, 6 out of 11 on insulin, and 4 out of 7 on both had diastolic dysfunction. This suggests that diastolic dysfunction is prevalent across all treatment groups, regardless of medication type.

In Madhumathi’s^[15] study, the duration of diabetes was significantly correlated with diastolic dysfunction, where 42% of patients had diabetes for less than 5 years, and 40% had diabetes for 5–10 years. In our study, we do not provide specific data on the correlation between the duration of diabetes and diastolic dysfunction. However, given the lower percentage of insulin use in our population, it may indicate that our cohort includes more patients with a shorter duration of diabetes or better-managed disease, as insulin use typically increases with the duration of diabetes.

Age, sex, region, and duration of diabetes all showed a significant relationship with the severity of diastolic dysfunction. Older individuals, females, and urban residents were at higher risk for more advanced stages of diastolic dysfunction. Glycemic control (HbA1c) was a key factor, with poorer control being strongly associated with more severe dysfunction. This highlights the importance of achieving good glycemic control to prevent cardiac complications. Triglyceride levels and BMI were also significantly associated with diastolic dysfunction, pointing to the importance of managing dyslipidemia and obesity in diabetic patients. Diabetic nephropathy, retinopathy and neuropathy were more prevalent in those with advanced diastolic dysfunction, indicating that cardiovascular and renal complications often coexist in diabetic populations

1. Savona-Ventura C. The history of diabetes mellitus-a Maltese perspective. Malta Limited Edition 2002:4-6.
2. Chan JC, Malik V, Jia W, Kadowaki T, Yajnik CS, Yoon KH, et al. Diabetes in Asia: epidemiology, risk factors, and pathophysiology. JAMA 2009;301(20):2129-40.
3. Warram JH, Andrzej Krolewski epidemiology of diabetes mellitus. In: Ronald Kahn C, ed. Joslin's diabetes mellitus. Lippincott Williams & Wilkins 2005.
4. Schneider BS, Faust IM, Hemmes R, Hirsch J. Effects of altered adipose tissue morphology on plasma insulin levels in the rat. American Journal of Physiology-Endocrinology and Metabolism 1981;240(4):E358-62.
5. Abate N, Garg A, Peshock RM, Stray-Gundersen J, Adams-Huet B, Grundy SM. Relationship of generalized and regional adiposity to insulin sensitivity in men with NIDDM. Diabetes 1996;45(12):1684-93.
6. Perin PC, Maule S, Quadri R. Sympathetic nervous system, diabetes, and hypertension. Clinical and Experimental Hypertension 2001;23(1-2):45-55.
7. Scherrer U, Sartori C. Insulin as a vascular and sympathoexcitatory hormone: implications for blood pressure regulation, insulinsensitivity, and cardiovascular Circulation 1997;96(11):4104-13.
8. Faden G, Faganello G, De Chiara B, Zardini P, Cardace G. Prevalence of left ventricular diastolic dysfunction in ambulatory hypertensive patients with well-controlled blood Journal of Hypertension 2008;26(11):2432-8.
9. Gupta S, Jain U, Chauhan SVS. Correlation of HbA1c with left ventricular diastolic dysfunction in type 2 diabetes Journal of Cardiovascular Disease Research 2015;6(3):217-22.
10. Maiello M, Cavallari I, Bellasi A, Garofalo M, Conte E. Association between obesity and diastolic dysfunction in women: a case-control study. Journal of Cardiovascular Disease Research 2016;7(1):22-9.
11. Kossaify A, Nicolas N, Koussa S. Impact of age on diastolic function in normal adults: a pulsed tissue Doppler echocardiographic Journal of Cardiovascular Ultrasound 2013;21(2):65-72.
12. Patil VC, Patil HV, Shah KB, Vasani JD, Shetty Diastolic dysfunction in asymptomatic type 2 diabetes mellitus with normal systolic function. Journal of Cardiovascular Disease Research 2011;2(4):213-22.
13. Rohinath K, Thanmaya SS, Kranthi. Correlation of HbA1c levels with left ventricular diastolic dysfunction in patients with type 2 diabetes mellitus” at a Government General Journal of Cardiovascular Disease Research 2024;5(7):1253-75.
14. Leung M, Wong VW, Hudson M, Leung DY. Impact of improved glycemic control on cardiac function in type 2 diabetes mellitus. Circulation: Cardiovascular Imaging 2016;9(3):e003643.
15. Madhumathi R, Gowdaiah PK, Dudhwewala A, Chaithra AN, Dande T. Echocardiographic evaluation of diastolic dysfunction in asymptomatic type 2 diabetes mellitus patients. Journal of Evolution of Medical and Dental Sciences 2014;3(1):200-9.