The authors have been committed to diabetic practice and research for a long time, in which we have developed low carbohydrate diet (LCD) measures for medical and healthcare regions [1,2]. Accordingly, several cases have shown remarkable weight reduction and diabetic improvement with three types of LCDs. They include super-LCD, standard-LCD, and petite-LCD, which indicate carbohydrate ratios of 12%, 26%, and 40%, respectively [3,4]. When diabetic patients reveal satisfactory weight reduction and pharmacological treatment, they seem to have remission for glucose variability. The latest topics concerning diabetic remission will be described in this article.

For the relationship between weight reduction and remission incidence, a total of 39676 type 2 diabetes (T2D) cases with ≥6.5% and/or prescribed oral hypoglycemic agents (OHAs) were investigated [5]. The follow-up period was long, from 1989 to 2022. Remission was defined as maintaining <6.5% of HbA1c at least 3 months after discontinuation of OHAs, and 3454 remissions were observed during the study. The remission incidence per 1000 person-years showed approximately 25 vs. 50 for cases with BMI reduction a year for 7.0-9.9% vs. ≥10% per 1 year. Weight reduction of 3.0-7.9% for modest degrees showed significant remission, and at least 10% weight reduction seemed to be necessary for achieving a 10% remission ratio in clinical practice.

Another large study was found for 48 thousand Japanese T2D patients for diabetic remission [6]. The total general remission incidence per 1000 person years showed 10.5. Three groups of T2D for i) 6.5-6.9% of HbA1c at baseline, ii) taking no OHAs, and iii) BMI reduction for ≥10% degree in 1 year showed an incidence of 27.8, 21.7, and 48.2, respectively. For two-thirds of the cases with remission (2490 out of 3677), they showed the relapse within 1 year. Concerning their background, significant related factors included lower BMI at baseline, longer duration, and lower BMI reduction.

A similar investigation was held in England during 2018–2019 [7]. The remission was diagnosed as two HbA1c values of <6.5% at least 6 months apart without OHAs for 3 months before the measurements. Among T2D cases (n = 2.3 million), the overall incidence of diabetic remission per 1000 person-years revealed 9.7, whereas cases (n = 75,610) diagnosed within 1 year showed 44.9. Concerning the higher remission odds, some factors are shorter duration after diagnosis, lower BMI, lower HbA1c, no OHAs at baseline, female sex, white ethnicity, and lower socioeconomic deprivation. When the remission cases were analyzed (n = 8940, 0.4%) with diagnosed <2 years, HbA1c <7.0%, taking only metformin, no OHAs or BMI reduction >10%, the calculated remission incidence showed 83.2 [78.7-87.9] per 1000 person-years. Consequently, T2D remission would be rare, but it can become a reasonable goal for T2D patients who can have a remarkable weight reduction shortly after diagnosis.

From a historical point of view, the Look AHEAD (Action for Health in Diabetes) study started formerly [8]. Patients with obesity or overweight were evaluated under the influence of a weight reduction program. In successive studies, cases with intensive lifestyle intervention showed a 20% lower risk for the primary outcome and a 21% lower risk for the secondary outcome [9]. These results of the post-hoc analysis suggested a possible relationship between weight reduction degree and CVD incidence for T2D patients.

The Look AHEAD study has been a multi-center RCT investigation that compared the efficacy of a 12-year intensive intervention for lifestyle. It analyzed diabetic support and education for cardiovascular disease (CVD) and other influences. In the latest study, the incidence of CVD and CKD was 4402 and 4132 cases, respectively [10]. They were based on the situation of diabetic remission in terms of duration and achievement. Participants showed 42% male, 59 years old, 6-year duration, and a BMI 35.8 kg/m², respectively. The remission was defined as HbA1c <6.5% and a medical history. High-risk CKD was defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Participants with remission during follow-up showed a 33% lower incidence of CKD (HR 0.67) and a 40% lower incidence of the composite CVD measure (HR 0.60), which was adjusted for diabetes duration, previous CVD history, BP, HbA1c, and lipids, compared with cases without remission.

In the latest study, a population-based observational investigation was found. It is the cohort study from Hong Kong for the Risk Assessment and Management Programme for Diabetes Mellitus (RAMP-DM) [11]. It shows comprehensive assessments of complication screening and metabolic control for diabetic patients. Totally 37 thousand new T2D cases were included for RAMP-DM during 2000–2017 and continued until 2019. Diabetic remission was found in 6.1% of cases with the achievement of remission, associated with an incidence ratio of 7.8 per 100 person-years. When comparing the patients who had weight gain, the adjusted HR for returning hyperglycemia showed 0.52 for cases with a weight reduction of ≥10%, 0.78 for cases with a weight reduction of 5.0-9.9%, and 0.90 for cases with a weight reduction of 0-4.9%. Diabetic remission was associated with a decreased risk for all-cause mortality of 31% (HR 0.69).

The Diabetes Remission Clinical Trial (DiRECT) has been a randomized controlled trial, and it revealed a weight management intervention. Weight reduction was 7.6 kg on average and was associated with remission in 36% of the T2D patients. Among them, 81% were in remission and maintained more than 10 kg of weight reduction for 2 years [12]. In successive 5 years, DiRECT extension cases showed a 6.1 kg reduction on average, associated with remission for 13% [13]. When compared with the non-extension category, the extension DiRECT category showed <6.5% of HbA1c (36% vs. 17%), no OHAs (62% vs. 30%), and remission state (34% vs. 12%), which are all significant differences.

As a related study of DiRECT in England, the DiRECT-Australia Type 2 Diabetes Remission Service was conducted in Sydney [14]. Two programs, 12-week and 52-week, were compared. Each protocol showed weight reduction as 12.0 kg vs. 9.1 kg, HbA1c decrease as 1.1% vs. 0.6%, and diabetic remission as 93.8% vs. 55.6%, respectively. Consequently, the scores of QOL and well-being increased during the 12 weeks and maintained a high degree for 52 weeks.

In summary, recent reports of diabetic remission have been shown from several perspectives. These data will contribute to the further development of treatments for weight reduction and HbA1c improvement in clinical practice in the future.

Conflict of interest: The authors declare no conflict of interest.

Funding: There was no funding received for this paper.

1. Wood M, Bando H, Ebe K. Beneficial Effects of Low Carbohydrate Diet (LCD) with Recently Emerged Solid Evidence. Asp Biomed Clin Case Rep. 2024; 7: 65-68.
2. Ebe K, Wood M and Bando H. Preventing Post-Prandial Elevation of Blood Glucose by Breakfast with Less Carbohydrate. Int J Case Rep Clin Image. 2024; 6: 219.
3. Bando H, Ebe K. Beneficial and Convenient Method of Low Carbohydrate Diet (LCD) as Petite, Standard and Super LCD. Asp Biomed Clin Case Rep. 2023; 7: 1-4.
4. Muneta T, Hayashi M, Nagai Y, Matsumoto M, Bando H, Ebe K, et al. Ketone Bodies in the Fetus and Newborn During Gestational Diabetes and Normal Delivery. Int J Diabetes. 2023; 5: 157-163.
5. Fujihara K, Khin L, Murai K, Yamazaki Y, Tsuruoka K, Yagyuda N, et al. Relationship between the magnitude of body mass index reductions and remission in patients with type 2 diabetes in real world settings: Analysis of nationwide patient registry in Japan (JDDM74). Diabetes Obes Metab. 2023; 25: 3125-3135.
6. Fujihara K, Khin L, Murai K, Yamazaki Y, Tsuruoka K, Yagyuda N, et al. Incidence and predictors of remission and relapse of type 2 diabetes mellitus in Japan: Analysis of a nationwide patient registry (JDDM73). Diabetes Obes Metab. 2023; 25: 2227-2235.
7. Holman N, Wild SH, Khunti K, Knighton P, O Keefe J, Bakhai C, et al. Incidence and Characteristics of Remission of Type 2 Diabetes in England: A Cohort Study Using the National Diabetes Audit. Diabetes Care. 2022; 45: 1151-1161.
8. Look AHEAD Research Group. Look AHEAD (Action for Health in Diabetes): design and methods for a clinical trial of weight loss for the prevention of cardiovascular disease in type 2 diabetes. Control Clin Trials. 2003; 24: 610-628.
9. Look AHEAD Research Group; Association of the magnitude of weight loss and changes in physical fitness with long-term cardiovascular disease outcomes in overweight or obese people with type 2 diabetes: a post-hoc analysis of the Look AHEAD randomised clinical trial. Lancet Diabetes Endocrinol. 2016; 4: 913-921.
10. Gregg EW, Chen H, Bancks MP, Manalac R, Maruthur N, Munshi M, et al. Impact of remission from type 2 diabetes on long-term health outcomes: findings from the Look AHEAD study. Diabetologia. 2024; 67: 459-469.
11. Wu H, Yang A, Lau ESH, Zhang X, Fan B, Ma RCW, et al. 1-year weight change after diabetes diagnosis and long-term incidence and sustainability of remission of type 2 diabetes in real-world settings in Hong Kong: An observational cohort study. PLoS Med. 2024; 21: e1004327.
12. Thom G, Messow CM, Leslie WS, Barnes AC, Brosnahan N, McCombie L, et al. Predictors of type 2 diabetes remission in the Diabetes Remission Clinical Trial (DiRECT). Diabet Med. 2021; 38: e14395.
13. Lean ME, Leslie WS, Barnes AC, Brosnahan N, Thom G, McCombie L, et al. 5-year follow-up of the randomised Diabetes Remission Clinical Trial (DiRECT) of continued support for weight loss maintenance in the UK: an extension study. Lancet Diabetes Endocrinol. 2024; 12: 233-246.
14. Chimoriya R, Mitlehner K, Khoo CL, Osuagwu UL, Thomson R, Si L, et al. Translation of a Diabetes Remission Service into Australian Primary Care: Findings from the Evaluation of DiRECT-Australia. J Diabetes Res. 2024; 2024: 2350551.