Lower fasting serum glucose
Fasting serum glucose levels decreased significantly from baseline in patients with type 2 diabetes after a PSMF in all studies that measured this variable.23–28,30,31 Changes in fasting glucose are immediate and are associated with caloric restriction rather than weight loss itself.30,32 Furthermore, the observed decrease in serum glucose is even more impressive in view of the withdrawal or reduction of doses of insulin and oral hypoglycemic agents before starting the diet.
In a study that compared glycemic control in a PSMF diet vs a balanced low-calorie diet, the fasting serum glucose in the PSMF group declined 46%, from 255.9 mg/dL at baseline to 138.7 mg/dL at 20 weeks (P = .001). After 1 year, it had risen back to 187.4 mg/dL, which was still 27% lower than at baseline (P = .023). These results compared favorably with those in the low-calorie diet group (P < .05), which saw fasting serum glucose decline 27% after 20 weeks (from 230.6 mg/dL at baseline to 167.6 mg/dL) and then rise to 5% over baseline (243.2 mg/dL) after 1 year.27
In a later study, the decrease in fasting serum glucose was not maintained at 1 year, but a significantly higher percentage (55%) of participants in the PSMF group were still able to remain free of diabetic medications compared with those who followed a balanced low-calorie diet (31%, P = .01).28
Decrease in hemoglobin A1c
Declines in fasting serum glucose corresponded with short-term declines in hemoglobin A1c in several reports.27–31 Hemoglobin A1c declined significantly from an average of 10.4% to 7.3% (P = .001) after PSMF intervention in patients with type 2 diabetes. In contrast, hemoglobin A1c in the low-calorie diet control group declined from 10.4% to 8.6%.27 One year later, hemoglobin A1c remained lower than at baseline in the PSMF group (final 9.2%) and continued to compare favorably against the control group (final 11.8%, between-group P = .001). However, these 1-year post-intervention improvements were not seen in a second, more intensive study.28
Less insulin resistance
In several studies, fasting serum insulin levels declined along with serum glucose levels, implying decreased insulin resistance.25,27,28,30,31 In addition, insulin output was enhanced during glucose challenge after completion of the PSMF, suggesting possible improved (though still impaired) pancreatic beta-cell capacity.25,27,30
Improved lipid profile
The most common effect of the PSMF on the lipid profile is a significant decrease in triglycerides in patients both with and without type 2 diabetes.8,23,24,28 In addition, high-density lipoprotein cholesterol increased in two studies following PSMF intervention or after 1-year of follow-up.24,27,28 Total cholesterol and low-density lipoprotein cholesterol levels also improved after the PSMF, but these changes were not always maintained at follow-up visits.8,24,28
Lower blood pressure
Improvements in both systolic and diastolic blood pressure were noted in two studies, with mean decreases of 6 mm Hg to 13 mm Hg systolic and 8 mm Hg diastolic after PSMF intervention.23,28 In a third study, reductions in blood pressure were less dramatic, and only changes in diastolic but not systolic blood pressure remained significant at 12 months.24 While improvements were not observed in a fourth study, patients in this study also had impaired kidney function caused by diabetic nephropathy, and changes in medication were not taken into account.31
Kidney function tests
In a small study, Friedman et al showed that 12 weeks of the PSMF in six patients with advanced diabetic nephropathy (stage 3B or stage 4 chronic kidney disease) led to a loss of 12% of body weight (P = .03) as well as significant reductions in serum creatinine and cystatin C levels (P < .05).31 In addition, albuminuria decreased by 30% (P = .08). Side effects were minimal, and the diet was well tolerated despite its high protein content, which is a concern in patients with impaired kidney function.
Thus, weight loss via the PSMF may still be beneficial in type 2 diabetic patients with chronic kidney disease and may even improve the course of progression of diabetic nephropathy.
Long-term weight loss is elusive
Long-term weight loss has been an elusive goal for many diet programs. In a study using a very-low-calorie diet in obese patients with type 2 diabetes, substantial weight loss was maintained in half of the patients at 3 years after the intervention, but nearly all of the patients had regained most of their weight after 5 years.33
While commitment to behavior modification, maintenance of physical activity, and continued follow-up are all critical factors in sustaining weight loss, new and innovative approaches to battle weight regain are needed.34
Yet despite considerable weight regain in most patients, the Look AHEAD (Action for Health in Diabetes) study showed that participants in intensive lifestyle intervention programs still achieved greater weight loss after 4 years than those receiving standard care.35 Whether this holds true for those in intensive PSMF programs is unknown. In addition, conclusive PSMF studies regarding glycemic control, lipids, and blood pressure beyond 1 year of follow-up are lacking.
A VIABLE OPTION FOR MANY
Adherence to a very-low-calorie, ketogenic PSMF program results in major short-term health benefits for obese patients with type 2 diabetes. These benefits include significant weight loss, often more than 18 kg, within 6 months.23–28 In addition, significant improvements in fasting glucose23–28,30–32 and hemoglobin A1c levels27–31 are linked to the caloric and carbohydrate restriction of the PSMF. Insulin resistance was also attenuated, with possible partial restoration of pancreatic beta-cell capacity.25,27,28,30,31 In some studies, the PSMF resulted in lower systolic and diastolic blood pressure23,24,28 and triglyceride levels.8,23,24,28 One small study also suggested a possible improvement of diabetic nephropathy.31 Lastly, improvements in glycemia and hypertension were associated with a reduction in the need for antidiabetic and antihypertensive drugs.36
Still, weight loss and many of the associated improvements partially return to baseline levels 1 year after the intervention. Thus, more long-term studies are needed to explore factors for better weight maintenance after the PSMF.
Also, only a few studies have compared the effect of the PSMF between patients with or without type 2 diabetes. One study suggested that fat loss may be reduced in patients with type 2 diabetes.26
In conclusion, despite some risks and safety concerns, PSMF is a viable option for many obese, type 2 diabetic patients as a method of short-term weight loss, with evidence for improvement of glycemic control and cardiovascular risk factors for up to 1 year. To strengthen support for the PSMF, however, further research is warranted on the diet’s long-term effects in patients with type 2 diabetes and also in nondiabetic patients.
Acknowledgments: Many thanks to Cheryl Reitz, RD, LD, CDE, and Dawn Noe, RD, LD, CDE, for providing their expertise on the PSMF protocols carried out at Cleveland Clinic. Additional thanks to Tejas Kashyap for his initial assistance with this review.