Metabolic Syndrome

Metabolic Syndrome, also known as Insulin Resistance Syndrome, is a cluster of conditions that are regularly seen in clinic. Usual care seems to be treating each of these symptoms of insulin resistance in a siloed or separate manner and fail to address the root cause of “the syndrome,” the insulin resistance. When a patients weight or waist has increased we tell them to “eat less and move more”, when they are hypertensive we prescribe an ACEi or ARB and tell them to avoid sodium and if their lipid profile is unhealthy we reinforce fat phobia and they are prescribed a statin and if they are pre-diabetic, providers often ignore this, fail to diagnose it and nothing may be done and we tell them “we will watch this” knowing full well the odds they will progress to type 2 diabetic are very highly probable (70% lifetime progression).

The position statement released by the AACE/ACE in November of 2018 clearly states that insulin resistance, prediabetes, T2D and cardiometabolic vascular complications are part of a 4 stage spectrum (11). Here at Restore we believe that hyperinsulinemia should be considered Stage 1a as hyperinsulinemia leads to insulin resistance (3,4). Pharmacological treatment of these symptoms of insulin resistance do little to nothing to address root causes and do little more than create a metabolic facade (1) of improved health by changing bio-markers. The patients unhealthy trajectory towards highly probable and unpleasant outcomes is slowed but not curbed. Patients must be made aware as to the very realistic endpoints they face if a pharmacological only care model is used. A pharmacological only care model may contribute to the individual’s lack of motivation to make positive lifestyle behavior changes that have the very real potential to curb this trajectory and alter these endpoints (1).

Well-established evidence suggests that insulin resistance is a common underpinning in many chronic health conditions including hypertension, T2D, CVD, PCOS, some cancers and Alzheimer’s disease (2, 10, 11). The evidence also suggests that these conditions associated with metabolic syndrome are the beginning of the pathology and not just risk factors (3, 11).

If root cause is to be addressed, providers must encourage treatment in the form of structured, on-going lifestyle modification (11), specifically diet, exercise, stress management and healthier habits that target triggers of hyperinsulinemia. Recent publications also suggests providers need to make “specific” recommendations or a referral to a “specific” intervention and avoid making general statements, such as, “you need to consider a diet and exercise regiment to lose weight” as these general recommendations have been shown to be ineffective (12). These modifications must begin sooner, rather than later if patients are to avoid the onset of these more serious and life threatening chronic health conditions (4, 5, 6, 7, 8, 11). A few words in clinic about the need to change and handout has proven to not be enough. Patients need referrals to structured, on-going programs. The development of any of the metabolic syndrome risk factors is a warning but two of the five risk factors associated with metabolic syndrome should be considered a sign that metabolic dysfunction has begun (3, 4, 8). A diagnosis of Metabolic or Insulin Resistance Syndrome is confirmed with the development of any 3 of the following 5:

  • Waist Circumference greater than 40 inches if you are male or 35 inches if you are female
  • Hypertension or are taking blood pressure medication
  • High blood sugar with either a high fasting blood sugar reading greater than 100 mg/dL or a diagnosis of pre-diabetes or diabetes
  • High blood triglycerides greater than 150 mg/dL or on lipid medication
  • Low HDL cholesterol, lower than 40 mg/dL if you are male or lower than 50 if you are female

Providers should be looking to identify these risk factors, and if seen, counsel patients on the need to change as soon as any of these conditions present. Providers should know that most patients will need to be supported during this modification process. A few words in clinic by the  provider with a handout or two will usually be unsuccessful in motivating or helping the patient be successful. Providers must make a strong statement regarding the need to change and use primary care-referable resources to help support patients during the change process if reversal of these conditions is to be expected (9).

Here at Restore Medical Fitness our programs drastically reduce the risk of, and in many cases reverse, metabolic syndrome. These patients are different from metabolically healthy individuals and need a modified way of eating to overcome their disease states. Patients that develop metabolic syndrome, in the majority of cases, and for the most part, are not suffering from a complete lack of self control and/or are lazy. Metabolically unhealthy, individuals in most cases, have an insulin resistant, hyperinsulinemic phenotype. They have a different phenotype than healthy lean individuals and need a way of eating that will not allow for the manifestation of obesity, diabetes, hypertension, dyslipidemia and metabolic syndrome. We have shown in hundreds of patients that this way of eating will place these conditions into remission. To simply define this way of eating it is real food, with little to no processing, with a very-low to low glycemic load and is very-low to low insulinogenic. Patients enrolled in our program achieve the following results in the first 12 weeks, on average:

  • Males with waist measurements of 40 or greater (n=104) lost 3.3 inches and females with waist measurements of 35 or greater (n=157) lost 3 inches.
  • Those with resting blood pressure over 120/80 (n=119) decrease resting blood pressure 11.4% with 40% of the 119 eliminating the need for hypertension medication.
  • Those with HbA1c of 5.7 or greater (n=164) decrease HbA1c 7.1% with over 60% of diabetics reducing or eliminating their need for glucose control medication.
  • Those with triglycerides of 150 or greater (n=108) reduced fasting triglycerides by 34.9%!
  • Males with HDL equal to or below 40 (n=54) increased HDL by 6.7% and females with HDL equal to or below 50 (n=72) increased HDL by 3.8%.


1 – Washburn, P.J., International Journal of User-Driven Healthcare, 6, 1, 2016 – Health Ballistics: Multiple Reference Point Informed Probability Theory

Conclusion: If an individual is afflicted with a chronic disease and does not know the realistic end point of their current health trajectory, they will never be fully ready, willing, motivated or able to make an informed, reliable, accurate and precise healthy behavioral decision in their current state of partially health informed reality. Alteration of health reality is accomplished by health informing the individual about the negatives of unhealthy behavior and the positives of healthy behavior.

2 – Crofts et. al., Diabesity 2015; 1 (4): 34-43 – Hyperinsulinemia: A unifying theory of chronic disease?

Concluding remarks: This review clearly demonstrates that not only is hyperinsulinemia involved with the etiology of all of the symptoms of metabolic syndrome, it is also implicated in many other conditions; some of which have previously been considered to be idiopathic, such as tinnitus. This raises many questions with both clinical and research implications. Firstly, what is the prevalence of hyperinsulinemia? Given its association with metabolic syndrome and fatty liver disease, this warrants investigation. Could early detection and careful management of hyperinsulinemia decrease the need for medical interventions later in life? Would managing hyperinsulinemia improve to both quantity and quality of life? Yet there are currently too many questions regarding diagnosis. A reliable and repeatable result when sampling insulin is still a challenging task. There is no agreed upon reference range, and there are only associations between quintiles and ongoing disease risk. Insulin response patterning may answer some of these questions, but patterning requires more resources than a fasting level. Given the global concerns about the ‘epidemic’ of metabolic diseases, this research needs to be urgently addressed.

3 – Joseph R, Kraft, MD, MS, FCAP 2008, 2011 Trafford Publishing – Diabetes Epidemic & You – Should everyone be tested? Absolutely NOT! Only those concerned about their future

From the back cover – “Normal blood sugar, normal weight, normal cholesterol do not exclude you from being a type 2 diabetic …one of the un-diagnosed millions! Yes- I do mean you!”

In this book Dr. Kraft outlines the evidence of over 14,000 OGTT’s with insulin assay. The evidence shows more than 50% of the adult population, even young adults, over produces insulin in response to excess carbohydrate consumption.

4- Crofts et al., Diabetes Research and Clinical Practice, 118 (2016) pp50-57 – Identifying hyperinsulinaemia in the absence of impaired glucose tolerance: An examination of the Kraft database

Conclusion: Hyperinsulinaemia in the absence of impaired glucose tolerance may provide the earliest detection for metabolic disease risk and likely occurs in a substantial proportion of an otherwise healthy population. Dynamic insulin patterning may produce more meaningful and potentially helpful diagnoses. Further research is needed to investigate clinically useful hyperinsulinaemia screening tools.

5 – Whaley-Connell et. al., CardioRenal Medicine, 2018;8:41-49 – Insulin Resistance in Kidney Disease: Is there a distinct role separate from that of diabetes or obesity?

Conclusions: In summary, it is clear that presence of the cardiorenal metabolic syndrome contributes to kidney injury and ultimately CKD. Experimental and clinical evidence support this relationship. In this regard, both insulin resistance and excess visceral adiposity contribute to maladaptive mechanisms in the kidney, including reductions in bioavailable NO that elicit attenuated tubuloglomerular feedback, hyperfiltration, and increased renal tubule sodium retention. They also promote glomerular mesangial expansion, glomerular hypertrophy, and kidney fibrosis that lead to the development of hypertension and albuminuria, all of which promote progression of kidney disease. Experimental models have dissected out the distinct pathways unique to both hyperinsulinemia (e.g., insulin resistance) and excess visceral adiposity (e.g., obesity) that contribute to kidney injury and disease. However, the clinical evidence is less clear. Smaller physiologic studies suggest a very real and direct negative renal impact of insulin resistance/hyperinsulinemia in eliciting kidney disease and vice versa. Yet, when looking at larger-database and prospective cohorts, it is less clear that there is a distinct role for insulin resistance independent of coexisting obesity or diabetes. Therefore, there is much work to be done to understand the metabolic relationships with CKD.

6 – Ohnishi et. al., Atherosclerosis 164 (2002) pp167-170 – Relationship between insulin-resistance and remnant-like particle cholesterol

Discussion: In this present study, a significant positive correlation was found between HOMA-R and RLP-C in the non-diabetic subjects and the value of RLP-C was found to be higher in the IR than in the normal group. Also, RLP-C was found to be closely related to IR regardless of age, sex, or BMI.
Although it is known that hypertriglyceridemia is one of the important component elements of IR syndrome, it is not known how hypertriglyceridemia is related to the development of atherosclerosis……

7 – Varbo et. al., Journal of the American College of Cardiology, 61, 4, 2013 – Remnant Cholesterol as a Causal Risk Factor for Ischemic Heart Disease

Conclusion: A nonfasting remnant cholesterol increase of 1 mmol/l (39 mg/dl) is associated with a 2.8-fold causal risk for ischemic heart disease, independent of reduced HDL cholesterol. This implies that elevated cholesterol content of triglyceride-rich  lipoprotein particles causes ischemic heart disease. However, because pleiotropic effects of the genetic variants studied cannot be totally excluded, these findings need to be confirmed using additional genetic variants and/or randomized intervention trials.

8 – Sagesaka et. al., Journal of the Endocrine Society, May 2018, 2, 5 – Type 2 Diabetes: When does it Start?

Conclusion: FPG was significantly elevated in those who developed diabetes at least 10 years before diagnosis of diabetes, and this was also the case in those who developed Pre-Diabetes Mellitus. Glucose dysregulation precedes diagnosis of diabetes at least for 20 years.

9 – Curry et. al., Annals of Internal Medicine, 160, 6, 2014 – Behavioral Counseling Research and Evidence-Based Practice Recommendations: U.S. Preventive Services Task Force Perspectives

Conclusion: Behavioral counseling interventions are important primary and secondary preventive care strategies, and the USPSTF is committed to developing and disseminating recommendations to ensure that effective interventions achieve the broadest reach into health care delivery. Effective synthesis and incorporation of evidence for behavioral counseling interventions into USPSTF recommendations is challenged by gaps in the current evidence base. The behavioral science community can better align primary care–based intervention studies with the key questions that guide the development of evidence-based recommendations. This commentary joins other voices calling for careful attention to study populations and the pragmatic aspects of intervention protocols in the design and dissemination of research, for greater consistency in key behavioral measures, and for further research that links behavior change to health outcomes.

10 – Xun et. al., American Journal of Clinical Nutrition, 2013;98: 1543-1554 – Fasting insulin concentration and incidence of hypertension, stroke and coronary heart disease: a meta-analysis of prospective cohort studies 1-3

Conclusions: A higher fasting insulin concentration or hyperinsulinemia was significantly associated with an increased risk of hypertension and CHD but not stroke. This meta-analysis suggests that early fasting insulin ascertainment in the general population may help clinicians identify those who are potentially at high risk of CVD.

11- Mechanick, J et. al., Endocrine Practice Vol 24 No. 11 November 2018 – Dysglycemia-Based Chronic Disease (DBCD): An American Association of Clinical Endocrinologists Position Statement

Conclusion: Recognizing and managing prediabetes is a necessary component for an effective personalized and population-based T2D care plan. In order to substantiate this position, AACE has formulated a DBCD multimorbidity care model consisting of four distinct stages in the general context of ABCD (adiposity based chronic disease) and cardiometabolic health and specific context along with insulin resistance-prediabetes-T2D spectrum that are actionable in a preventive care paradiagm.

12 – McVay, et. al., Journal of General Internal Medicine – March 2019 – Provider Counseling and Weight Loss Outcomes in a Primary Care-Based Digital Obesity Treatment

Key Results:

Participants (n = 134–141) were predominantly female (70%) and African American (55%) with a mean age of 51 years and BMI of 36 kg/m2. Participant-reported provider weight counseling was not associated with weight change. However, participants whose providers documented intervention-specific counseling at any point during the intervention (n = 35) lost 3.1 kg (95% CI 0.4 to 5.7 kg) more than those whose providers documented only general weight counseling (n = 82) and 4.0 kg (95% CI 0.1 to 7.9 kg) more than those whose providers did not document weight counseling (n = 17). Perceptions of provider empathy were associated with greater weight loss from 6 to 12 months (0.8 kg per measure unit, 95% CI 0.07 to 1.5 kg, p = .03).