Diabetic cardiomyopathy: Pathophysiology, theories and evidence to date

Table 1 Myocardial triglyceride content in type 2 diabetes

Study details (Author,Year)	Sample population	Exclusion	Results
Jankovic et al[92], 2012	n = 18	Previous MI, CAD, HF, digitalis use or thiazolidinediones, previous insulin use or T1D	Baseline IT myocardial lipid content 0.42% ± 0.12% vs 0.80% ± 0.11% water signal, (aP = 0.034).
	IT (n = 10)
	Mean age 56 ± 2	Patients on insulin must have had insufficient control on oral, HbA1C > 8% and on oral therapy	Myocardial lipid content decreased by 80% after 10 d IT (P = 0.008). No significant change in hepatic lipid content. After 181 ± 49 d, myocardial lipid content returned to baseline (0.37 ± 0.06, P = 0.692) Hepatic lipid content decreased by 31% (bP < 0.001)
	DM duration 9 ± 2 yr
	6 males
	HbA1c 11.1 ± 0.4
	Oral therapy (OT) (n = 8)
	Mean age 53 ± 2
	DM duration 3 ± 1 yr
	4 males
	HbA1c 9.8% ± 0.7%
Korosoglou et al[119], 2012	n = 58	Unstable condition, clinical signs of heart failure or angina contraindications for CMR, insulin use	Significant association between myocardial triglyceride content and mean diastolic strain rate (r = -0.71, cP < 0.001) and no association was found between triglyceride content and perfusion reserve (r = -0.08, P = NS)
	T2D (n = 42)
	Mean age 62 ± 6 yr
	26 male
	Mean BMI 31.6 ± 4.8 kg/m2
	HV (n = 16)
	Mean age 62 ± 3 yr
	10 male
	Mean age 62 ± 3 yr
	Mean BMI 23.9 ± 2.5
Van der Meer et al[101,155], 2009	n = 72 T2D	BP > 150/85 mmHg, previous insulin or thiazolidinedione use, previous positive stress echo or arrhythmia, diabetes related complications or significant medical problems	No significant change in myocardial fatty acid uptake at follow up on either arm. Metformin arm showed a significant decrease in fatty acid oxidation and myocardial glucose uptake. No significant change in myocardial triglyceride content in Pioglitazone or Metformin arm after therapy however there was a decrease in hepatic triglyceride content in the Pioglitazone arm
	All males
	Pioglitazone (n = 39)
	Metformin (n = 39)
	Baseline age 45-65
	HbA1C 6.5%-8.5%
	BMI 25-32
Rijzewijk et al[83], 2008	n = 66	Females, HbA1C > 8.5%, BP > 150/80, hepatic impairment or history of liver disease, substance abuse, known CVD, DM complications, contraindication to MRI, use of lipid lowering therapy.	Myocardial triglyceride content  in T2D vs controls (0.96% ± 0.07% vs 0.65% ± 0.05%). Hepatic triglyceride content  in T2D vs controls (8.6% vs 2.2%). Both cases, dP < 0.05 On univariate analysis, myocardial triglyceride content correlated with age, visceral adipose tissue, cholesterol, plasma glucose and insulin and hepatic triglyceride content (eP < 0.05 for all). E/A independently associated with myocardial triglyceride content on multivariate analysis (inverse correlation)
	T2D (n = 38)
	All males
	mean age 57 ± 1 yr
	BMI: 28.1 ± 0.6
	Controls (n = 28)
	All males
	Mean Age: 54 ± 1
	BMI: 26.9 ± 0.5
McGavock[82] 2007	n = 134	Age > 70 yr, known CAD, Previous MI, contraindications to MRI, thiazolidinedione treatment	↑Subcutaneous, visceral fat and hepatic triglyceride in O,I and T2D vs L, ↑myocardial triglyceride content in I and DM vs L (0.95 ± 0.60 vs 1.06 ± 0.62 vs 0.46 ± 0.30 fat/water content, fP < 0.05), this remained significant after adjusted for serum triglyceride, BMI, age and gender. In multiple regression model, Subcutaneous and visceral fat both independent determinants of myocardial triglyceride content (gP < 0.05) however myocardial triclyceride unrelated to hepatic triglyceride or diastolic function
	Lean(L) (n = 15)
	Age 35 ± 3 yr, 47% males
	BMI 23 ± 2, non T2D
	Overweight/Obese(O): (n = 21) Age 36 ± 12, BMI 32 ± 5, 48% males , non T2D
	Impaired glucose tolerance(I): (n = 20)
	Age 49 ± 9, 25% males, BMI 31 ± 6,
	T2D (n = 78),
	Age 47 ± 10, 47% males BMI 34 ± 7

DM: Diabetes mellitus; MI: Myocardial infarction; T1D: Type 1 diabetic; CAD: Coronary artery disease; BMI: Body mass index; IT: Insulin therapy.