Nwosu BU, Zhang B, Ayyoub SS, et al. Children with type 1 diabetes who experienced a honeymoon phase had significantly lower LDL cholesterol 5 years after diagnosis. PLoS One. 2018;13(5):e0196912.
To determine if there are any differences in low-density lipoprotein cholesterol (LDL-C) between children who underwent partial remission (remitters) and those who did not (nonremitters) 4 to 5 years after the diagnosis of type 1 diabetes.
Longitudinal retrospective cohort study
The study included 123 children, mean age 11.9 ± 2.9 years (male 11.7 ± 2.9 years [n=55]; female 12.0 ± 2.9 years [n=68]; P=0.60), with type 1 diabetes of 4 to 5 years’ duration.
Study Parameters Assessed
Anthropometric and biochemical data, including lipid parameters, were collected at the 4th or 5th year after diagnosis, in line with the American Diabetes Association recommendation to initiate screening for complications in children either at the beginning of puberty or 4 to 5 years after diagnosis. Puberty was defined by Tanner stages II-V. Partial clinical remission was defined by the gold-standard insulin dose–adjusted hemoglobin A1c (IDAA1c) of ≤9. Children who achieved partial clinical remission were considered remitters.
Primary Outcome Measure
Level of LDL-C 4 to 5 years after diagnosis of type 1 diabetes.
There were 44 (35.8%) remitters (age 13.0 ± 2.5 y; male 52.3%). Both the total cholesterol and LDL-C were significantly lower in remitters compared to nonremitters (total cholesterol: 151.5 ± 32.6 mg/dL vs 167.0 ± 29.6 mg/dL; P=0.015 and LDL-C: 78.8 ± 28.7 mg/dL vs 91.6 ± 26.5 mg/dL; P=0.023). Other lipid fractions were similar between the groups. There were no differences between the groups for glycemic control, BMI z score, thyroid function, celiac disease occurrence, or vitamin D status.
A greater number of remitters were in puberty compared to nonremitters (86.4% vs 60.8%; P=0.006). Concentration of LDL-C was similar in prepubertal remitters vs nonremitters (P=0.93), but was significantly lower in remitters in puberty compared to nonremitters in puberty (P=0.018) after adjusting for age and duration of diabetes.
Partial clinical remission in new-onset type 1 diabetics, also called the honeymoon period, is associated with reduced prevalence of long-term complications.1 In this study, children with type 1 diabetes who underwent a honeymoon phase (remitters) had significantly lower LDL-C 5 years after diagnosis. This early divergence in lipidemia may explain the dichotomy in the prevalence of long-term complications in type 1 diabetes between remitters and nonremitters. It also offers a pathway for targeted lipid monitoring in type 1 diabetes, by establishing nonremission as a nonmodifiable risk factor for vascular complication in type 1 diabetes.
In addition to the findings in this study, other prospective studies also confirm that retaining a degree of endogenous beta-cell function for 5 or more years after diagnosis is associated not only with a reduced incidence of long-term complications, but also lower glycated hemoglobin A1c levels, and less hypoglycemia.2,3 Given this, it behooves us to look at what steps can be taken to preserve beta-cell function.
Beta-cell preservation in newly diagnosed type 1 diabetes is not a topic discussed in conventional medicine. Indeed, research is limited, but there is some evidence showing certain steps can preserve residual beta-cell function in those who still have some function.4
Based on current evidence, maintaining normal blood sugars is the most important step for protecting beta cells.
Upon diagnosis of classic-onset type 1 disease, it is estimated that 5% to 20% of beta-cell mass remains. In latent autoimmune diabetes in adulthood (LADA, also referred to as type 1.5) there is often an even larger degree of beta-cell function left.5 Standard predictions are that this honeymoon period will only last a few months, or maximum of a year. In my experience, when patients take specific steps to preserve beta-cell function, the “honeymoon” can last longer.
There is not enough long-term data to make any promises or predictions about how long the honeymoon can be extended. However, the study under review here implies that long-term health risks of diabetes may be mitigated in those who experience this honeymoon phase. With this in mind, the following is an approach for clinicians to consider when caring for patients with newly diagnosed type I diabetes, in particular.
First, how do you know if beta cells are still working? Beta-cell function can be assessed by measuring circulating C-peptide, a test available at any standard lab. However, if the patient is injecting insulin, the insulin will have a suppressive effect on beta-cell function, thus rendering the test inaccurate. Having said that, even with the presence of injected insulin, as long as the C-peptide is not zero, that means the beta cells are still active, because the only way to have any degree of C-peptide circulating is from endogenous insulin production.
Tracking the C-peptide every 3 to 6 months while taking steps to preserve beta-cell function is prudent. Serial testing should be done while fasting, and ideally, without any injected insulin in the body. However, avoiding injected insulin may not be possible in some patients due to risk of diabetic ketoacidosis. If this is the case, try to keep the basal insulin amount consistent at the time of each test.
Keep blood sugars as normal as possible
Current data suggest that chronically high glucose levels may impair insulin synthesis/secretion, beta-cell survival, and insulin sensitivity,6 and lead to irreversible cellular dysfunction, a process that is termed glucose toxicity.7 Hyperglycemia is equivalent to an HbA1c of 5.7% or above, which equates to an average glucose above 117 mg/dL (or 6.5 mmol/L). Putting these facts together, it makes sense that maintaining tight glucose control, with readings between 70 and 120 mg/dL (3.8 - 6.6 mmol/L) as much as possible, 24 hours a day, including fasting, before meals and after meals, would be advisable to protect beta cells and promote survival. High blood sugars themselves are toxic to beta cells, and they also put extra demands on them. Based on current evidence, maintaining normal blood sugars is the most important step for protecting beta cells.
Eat a low-carbohydrate diet
Although management of diabetes with a low-carbohydrate diet has been challenged over the years, a recent critical review provides convincing evidence to support low-carb diets as a means of maintaining tight glucose control.8 A 2018 paper in the journal Pediatrics observed exceptional glucose control in a population of patients with type 1 disease who consumed a very low–carbohydrate diet.9 I suggest a maximum of 25 g of LOW-glycemic carbohydrates at any one time. The higher glycemic the food, the more it should be kept to a minimum.
In regards to gluten, studies are mixed. Some suggest a gluten-free diet may preserve beta cell function, but others have not found this effect. One study in infants showed amount, timing, and mode of introduction were shown to affect the diabetogenic potential of gluten. In non-obese diabetic mice, a gluten-free diet largely prevents diabetes while cereal-based diets promote it.10 If a patient is motivated to preserve beta cells, I suggest a gluten-free diet.
Research is limited on the topic of supplements to protect beta cells, and the studies that do exist show mixed results. The following is a short list of supplements to consider.
A 2013 study from the Harvard School of Public Health provides the strongest findings to date to suggest that vitamin D may be protective against type 1 diabetes. Investigators found that adequate levels of vitamin D during young adulthood may reduce the risk of adult-onset type 1 diabetes by as much as 50%.11
Omega-3 fatty acids
A 2007 study published in JAMA found that dietary intake of omega-3 fatty acids is associated with reduced risk of islet-cell auto-immunity in children at increased genetic risk for type 1 diabetes. The authors hypothesize that the benefits may come from the antiinflammatory actions of docosahexaenoic acid (DHA; a component of fish oil).12 Therefore, fish oils may help by inhibiting inflammation-related beta-cell damage.
The findings to support nicotinamide as beta-cell–protective are mixed. According to a 2006 study, low doses of nicotinamide may reduce insulin requirements, prolonging the honeymoon period for up to 2 years after diagnosis,13 findings supported by an earlier study in the European Journal of Endocrinology.14 However, other research has shown it not to be effective.15
Gymnema sylvestre leaf extract
Results of small study (N=27) of patients taking 400 mg/day of Gymnema sylvestre extract (GS4) suggested that GS4 may possibly regenerate/revitalize residual beta-cell function in insulin-dependent diabetes mellitus.16 Doses up to 2,250 mg/day have been used. Dosing should be adjusted based on age and weight.
Green tea is a great antioxidant, and there is evidence that it can protect the body against the damage caused by high blood sugar levels. A study in genetically diabetic mice showed that green tea preserves islet structure and enhances glucose tolerance.17
Exercise, especially with weight training
Muscles eat up glucose at a higher rate during exercise, but also even during sleep. The more muscle mass, the more glucose can be taken up, thus the less insulin the beta cells need to fight to make. Having good muscle tone takes stress off the beta cells because muscles can take in glucose in the absence of insulin.
Optimize gut health
With type 1 diabetes, many possible causative factors have been studied, such as vitamin D status, recent viral infection, the health of the microbiome, history of breastfeeding, age when cow’s milk was introduced, the mother's health during pregnancy, vaccinations, nutrient deficiencies, environmental toxin exposure, and more. Regardless, the health of the gut has been strongly correlated with the health of the immune system. When gut health is not good there is greater risk of autoimmune disease.18
In 2009 a paper titled “The Importance Of Endogenous Beta-Cell Preservation In Type 1 Diabetes” was published in The British Journal of Diabetes & Vascular Disease. In it, the authors assert, “Retention of even small amounts of endogenous beta-cell function for as long as possible should therefore be a key therapeutic goal in type 1 diabetes.”2 Here we are a decade later, and the sentiment is as true as ever.
- Steffes MW, Sibley S, Jackson M, Thomas W. Beta-cell function and the development of diabetes-related complications in the diabetes control and complications trial. Diabetes Care. 2003;26(3):832-836.
- Ali MA, Dayan CM. Review: the importance of residual endogenous beta-cell preservation in type 1 diabetes. Br J Diabetes Vasc Dis. 2009;9(6):248-253.
- Sørensen JS, Johannesen J, Pociot, et al; Danish Society for Diabetes in Childhood and Adolescence. Residual β-Cell function 3-6 years after onset of type 1 diabetes reduces risk of severe hypoglycemia in children and adolescents. Diabetes Care. 2013;36(11):3454-3459.
- Klinke DJ. Extent of beta cell destruction is important but insufficient to predict the onset of type 1 diabetes mellitus. PLoS One. 2008;3(1):e1374.
- Stenström G, Gottsäter, A, Bakhtadze E, Berger B, Sundkvist G. Latent autoimmune diabetes in adults. Diabetes. 2005;54(suppl 2):S68-S72.
- Cernea S, Dobreanu M. Diabetes and beta cell function: from mechanisms to evaluation and clinical implications. Biochem Med (Zagreb). 2013;23(3):266-280.
- Robertson RP, Harmon J, Tran PO, Tanaka Y, Takahashi H. Glucose toxicity in beta-cells: type 2 diabetes, good radicals gone bad, and the glutathione connection. Diabetes. 2003;52(3):581-587.
- Feinman RD, Pogozelski WK, Astrup A, et al. Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base. Nutrition. 2015;31(1):1-13.
- Lennerz BS, Barton A, Bernstein RK, et al. Management of type 1 diabetes with a very low–carbohydrate diet. Pediatrics. 2018;141(6):e20173349.
- Munger KL, Levin LI, Massa J, Horst R, Orban T, Ascherio A. Preclinical serum 25-hydroxyvitamin d levels and risk of type 1 diabetes in a cohort of us military personnel. Am J Epidemiol. 2013;177(5):411-419.
Antvorskov JC, Josefsen K, Engkilde K, Funda DP, Buschard K.Dietary gluten and the development of type 1 diabetes. Diabetologia. 2014;57(9):1770-1780.
- Norris JM, Yin X, Lamb MM, et al. Omega-3 polyunsaturated fatty acid intake and islet autoimmunity in children at increased risk for type 1 diabetes. JAMA. 2007;298(12):1420-1428.
- Kamal M, Abbasy AJ, Muslemani AA, Bener A. Effect of nicotinamide on newly diagnosed type 1 diabetic children. Acta Pharmacol Sin. 2006;27(6):724-727.
- Crinò A, Schiaffini R, Manfrini S, et al; IMDIAB group. A randomized trial of nicotinamide and vitamin E in children with recent onset type 1 diabetes (IMDIAB IX). Eur J Endocrinol. 2004;150(5):719-724.
- Gale EA, Bingley PJ, Emmett CL, Collier T; European Nicotinamide Diabetes Intervention Trial (ENDIT) Group. European Nicotinamide Diabetes Intervention Trial (ENDIT): a randomised controlled trial of intervention before the onset of type 1 diabetes. Lancet. 2004;363(9413):925-931.
- Shanmugasundaram ER, Rajeswari G, Baskaran K, Rajesh Kumar BR, Radha Shanmugasundaram K, Kizar Ahmath B. Use of Gymnema sylvestre leaf extract in the control of blood glucose in insulin-dependent diabetes mellitus. J Ethnopharmacol. 1990;30(3):281-294.
- Ortsäter H, Grankvist N, Wolfram S, Kuehn N, Sjöholm A. Diet supplementation with green tea extract epigallocatechin gallate prevents progression to glucose intolerance in db/db mice. Nutr Metab (Lond). 2012;9:11.
- Mariño E, Richards JL, McLeod KH, et al. Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes. Nat Immunol. 2017;18(5):552-562.