Table 1.
Unique features of the diabetic heart and distinct effects of sex and types of diabetes on cardiac metabolism
| Diabetic Heart | Failing Heart | References | |
|---|---|---|---|
| Cardiac uptake of ketone body | Higher than non-DM | Lower than DM | (5) |
| Ketogenic enzyme HMGCS2 | Increased transcription | Decreased transcription | (6–8) |
| Fatty acid oxidation | High | Low | (9) |
| T1DM heart | T2DM heart | ||
|---|---|---|---|
| Insulin levels | Low | High | |
| Ketone body levels | 10-fold higher levels of β-hydroxybutyrate than non-DM | Lower than T1DM because insulin suppresses HMGCS2 to inhibit ketogenesis | (10–12) |
| Hmgcs2 mRNA | 10-fold elevation than non-DM | No difference than non-DM | (10) |
| Ketone body transporters (solute carrier 16A family) | No change in Slc16a1 and Slc16a7 than non-DM | No change in Slc16a1 and Slc16a7 than non-DM | (10) |
| Ketolysis gene BDH1 expression | Bdh1 mRNA reduced 50%, BDH1 activity reduced 27% than non-DM | Bdh1 mRNA reduced 47%, BDH1 activity reduced 67% than non-DM | (10, 13) |
| Ketolysis gene Oxct1/SCOT expression | Oxct1 reduced ∼24%, no change in SCOT activity compared with non-DM | Oxct1 reduced ∼24%, no change in SCOT activity compared with non-DM | (10) |
| Female DM heart | Male DM heart | ||
|---|---|---|---|
| Prevalence of DM | 9% | 9.6% | (14) |
| Myocardial steatosis | Higher than males | Lower than females | (16) |
| Risk of congestive heart failure | ∼3-fold higher than males (age 45–74 yr) | Lower than females | (17) |
| Risk of cardiovascular complications | Higher in females compared with males | Lower compared with females | Table 1 of (14) |
| Prediabetes (fasting plasma glucose levels 110–125 mg/dL) cardiovascular disease risk | Higher | No effect | (18) |
| Heart failure compared with healthy | 5-fold higher | 2.4-fold higher | (19) |
| Predisposition to heart failure with preserved ejection fraction | High | Low | (20) |
| Prevalence of DMCM | Higher than males | Lower than females | (21, 22) |
| T2DM prevalence | Lower than males | Higher than females | (22) |
| Weight loss effects on glucose levels and insulin resistance | Fewer effects than male | Higher effects than females | (23) |
| Antidiabetic drug effectiveness | Higher than males | Lower than females | (24) |
| Effect of insulin on cardiac mitochondrial respiration in STZ-induced T1DM | Higher than males leading to increased risk of heart failure | Lower than female | (25) |
| Female heart | Male heart | ||
|---|---|---|---|
| Ketogenesis | 2.86-fold higher than males | Lower than females | (26) |
| Mitochondria number and efficiency in cardiomyocytes | Fewer in number but more efficient | More in number but less efficient | (27, 28) |
BDH1, β-hydroxybutyrate dehydrogenase-1; DM, diabetes mellitus; DMCM, diabetic cardiomyopathy; HMGCS2, 3-hydroxy-3-methylglutaryl-CoA-synthase 2; Oxct1, 3-oxoacid CoA-transferase 1; SCOT, succinyl-CoA:3-ketoacid CoA transferase; STZ, streptozotocin.